MicroRNA-335-5p is a potential suppressor of metastasis and invasion in gastric cancer

Background Multiple aberrant microRNA expression has been reported in gastric cancer. Among them, microRNA-335-5p (miR-335), a microRNA regulated by DNA methylation, has been reported to possess both tumor suppressor and tumor promoter activities. Results Herein, we show that miR-335 levels are reduced in gastric cancer and significantly associate with lymph node metastasis, depth of tumor invasion, and ultimately poor patient survival in a cohort of Amerindian/Hispanic patients. In two gastric cancer cell lines AGS and, Hs 746T the exogenous miR-335 decreases migration, invasion, viability, and anchorage-independent cell growth capacities. Performing a PCR array on cells transfected with miR-335, 19 (30.6%) out of 62 genes involved in metastasis and tumor invasion showed decreased transcription levels. Network enrichment analysis narrowed these genes to nine (PLAUR, CDH11, COL4A2, CTGF, CTSK, MMP7, PDGFA, TIMP1, and TIMP2). Elevated levels of PLAUR, a validated target gene, and CDH11 were confirmed in tumors with low expression of miR-335. The 3′UTR of CDH11 was identified to be directly targeted by miR-335. Downregulation of miR-335 was also demonstrated in plasma samples from gastric cancer patients and inversely correlated with DNA methylation of promoter region (Z = 1.96, p = 0.029). DNA methylation, evaluated by methylation-specific PCR assay, was found in plasma from 23 (56.1%) out of 41 gastric cancer patients but in only 9 (30%) out of 30 healthy donors (p = 0.029, Pearson’s correlation). Taken in consideration, our results of the association with depth of invasion, lymph node metastasis, and poor prognosis together with functional assays on cell migration, invasion, and tumorigenicity are in accordance with the downregulation of miR-335 in gastric cancer. Conclusions Comprehensive evaluation of metastasis and invasion pathway identified a subset of associated genes and confirmed PLAUR and CDH11, both targets of miR-335, to be overexpressed in gastric cancer tissues. DNA methylation of miR-335 may be a promissory strategy for non-invasive approach to gastric cancer. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Sandoval-Bórquez, Alejandra [verfasserIn] Polakovicova, Iva Carrasco-Véliz, Nicolás Lobos-González, Lorena Riquelme, Ismael Carrasco-Avino, Gonzalo Bizama, Carolina Norero, Enrique Owen, Gareth I. Roa, Juan C. Corvalán, Alejandro H.

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2017

Schlagwörter:	miR-335 Gastric cancer Metastasis PLAUR CDH11 Methylation

Anmerkung:	© The Author(s). 2017

Übergeordnetes Werk:	Enthalten in: Clinical epigenetics - [S.l.] : BioMed Central, 2010, 9(2017), 1 vom: 17. Okt.
Übergeordnetes Werk:	volume:9 ; year:2017 ; number:1 ; day:17 ; month:10

Links:	Volltext

DOI / URN:	10.1186/s13148-017-0413-8

Katalog-ID:	SPR03067557X

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520			\|a Background Multiple aberrant microRNA expression has been reported in gastric cancer. Among them, microRNA-335-5p (miR-335), a microRNA regulated by DNA methylation, has been reported to possess both tumor suppressor and tumor promoter activities. Results Herein, we show that miR-335 levels are reduced in gastric cancer and significantly associate with lymph node metastasis, depth of tumor invasion, and ultimately poor patient survival in a cohort of Amerindian/Hispanic patients. In two gastric cancer cell lines AGS and, Hs 746T the exogenous miR-335 decreases migration, invasion, viability, and anchorage-independent cell growth capacities. Performing a PCR array on cells transfected with miR-335, 19 (30.6%) out of 62 genes involved in metastasis and tumor invasion showed decreased transcription levels. Network enrichment analysis narrowed these genes to nine (PLAUR, CDH11, COL4A2, CTGF, CTSK, MMP7, PDGFA, TIMP1, and TIMP2). Elevated levels of PLAUR, a validated target gene, and CDH11 were confirmed in tumors with low expression of miR-335. The 3′UTR of CDH11 was identified to be directly targeted by miR-335. Downregulation of miR-335 was also demonstrated in plasma samples from gastric cancer patients and inversely correlated with DNA methylation of promoter region (Z = 1.96, p = 0.029). DNA methylation, evaluated by methylation-specific PCR assay, was found in plasma from 23 (56.1%) out of 41 gastric cancer patients but in only 9 (30%) out of 30 healthy donors (p = 0.029, Pearson’s correlation). Taken in consideration, our results of the association with depth of invasion, lymph node metastasis, and poor prognosis together with functional assays on cell migration, invasion, and tumorigenicity are in accordance with the downregulation of miR-335 in gastric cancer. Conclusions Comprehensive evaluation of metastasis and invasion pathway identified a subset of associated genes and confirmed PLAUR and CDH11, both targets of miR-335, to be overexpressed in gastric cancer tissues. DNA methylation of miR-335 may be a promissory strategy for non-invasive approach to gastric cancer.
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allfields	10.1186/s13148-017-0413-8 doi (DE-627)SPR03067557X (SPR)s13148-017-0413-8-e DE-627 ger DE-627 rakwb eng Sandoval-Bórquez, Alejandra verfasserin aut MicroRNA-335-5p is a potential suppressor of metastasis and invasion in gastric cancer 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Multiple aberrant microRNA expression has been reported in gastric cancer. Among them, microRNA-335-5p (miR-335), a microRNA regulated by DNA methylation, has been reported to possess both tumor suppressor and tumor promoter activities. Results Herein, we show that miR-335 levels are reduced in gastric cancer and significantly associate with lymph node metastasis, depth of tumor invasion, and ultimately poor patient survival in a cohort of Amerindian/Hispanic patients. In two gastric cancer cell lines AGS and, Hs 746T the exogenous miR-335 decreases migration, invasion, viability, and anchorage-independent cell growth capacities. Performing a PCR array on cells transfected with miR-335, 19 (30.6%) out of 62 genes involved in metastasis and tumor invasion showed decreased transcription levels. Network enrichment analysis narrowed these genes to nine (PLAUR, CDH11, COL4A2, CTGF, CTSK, MMP7, PDGFA, TIMP1, and TIMP2). Elevated levels of PLAUR, a validated target gene, and CDH11 were confirmed in tumors with low expression of miR-335. The 3′UTR of CDH11 was identified to be directly targeted by miR-335. Downregulation of miR-335 was also demonstrated in plasma samples from gastric cancer patients and inversely correlated with DNA methylation of promoter region (Z = 1.96, p = 0.029). DNA methylation, evaluated by methylation-specific PCR assay, was found in plasma from 23 (56.1%) out of 41 gastric cancer patients but in only 9 (30%) out of 30 healthy donors (p = 0.029, Pearson’s correlation). Taken in consideration, our results of the association with depth of invasion, lymph node metastasis, and poor prognosis together with functional assays on cell migration, invasion, and tumorigenicity are in accordance with the downregulation of miR-335 in gastric cancer. Conclusions Comprehensive evaluation of metastasis and invasion pathway identified a subset of associated genes and confirmed PLAUR and CDH11, both targets of miR-335, to be overexpressed in gastric cancer tissues. DNA methylation of miR-335 may be a promissory strategy for non-invasive approach to gastric cancer. miR-335 (dpeaa)DE-He213 Gastric cancer (dpeaa)DE-He213 Metastasis (dpeaa)DE-He213 PLAUR (dpeaa)DE-He213 CDH11 (dpeaa)DE-He213 Methylation (dpeaa)DE-He213 Polakovicova, Iva aut Carrasco-Véliz, Nicolás aut Lobos-González, Lorena aut Riquelme, Ismael aut Carrasco-Avino, Gonzalo aut Bizama, Carolina aut Norero, Enrique aut Owen, Gareth I. aut Roa, Juan C. aut Corvalán, Alejandro H. aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 9(2017), 1 vom: 17. Okt. (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:9 year:2017 number:1 day:17 month:10 https://dx.doi.org/10.1186/s13148-017-0413-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2017 1 17 10
spelling	10.1186/s13148-017-0413-8 doi (DE-627)SPR03067557X (SPR)s13148-017-0413-8-e DE-627 ger DE-627 rakwb eng Sandoval-Bórquez, Alejandra verfasserin aut MicroRNA-335-5p is a potential suppressor of metastasis and invasion in gastric cancer 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Multiple aberrant microRNA expression has been reported in gastric cancer. Among them, microRNA-335-5p (miR-335), a microRNA regulated by DNA methylation, has been reported to possess both tumor suppressor and tumor promoter activities. Results Herein, we show that miR-335 levels are reduced in gastric cancer and significantly associate with lymph node metastasis, depth of tumor invasion, and ultimately poor patient survival in a cohort of Amerindian/Hispanic patients. In two gastric cancer cell lines AGS and, Hs 746T the exogenous miR-335 decreases migration, invasion, viability, and anchorage-independent cell growth capacities. Performing a PCR array on cells transfected with miR-335, 19 (30.6%) out of 62 genes involved in metastasis and tumor invasion showed decreased transcription levels. Network enrichment analysis narrowed these genes to nine (PLAUR, CDH11, COL4A2, CTGF, CTSK, MMP7, PDGFA, TIMP1, and TIMP2). Elevated levels of PLAUR, a validated target gene, and CDH11 were confirmed in tumors with low expression of miR-335. The 3′UTR of CDH11 was identified to be directly targeted by miR-335. Downregulation of miR-335 was also demonstrated in plasma samples from gastric cancer patients and inversely correlated with DNA methylation of promoter region (Z = 1.96, p = 0.029). DNA methylation, evaluated by methylation-specific PCR assay, was found in plasma from 23 (56.1%) out of 41 gastric cancer patients but in only 9 (30%) out of 30 healthy donors (p = 0.029, Pearson’s correlation). Taken in consideration, our results of the association with depth of invasion, lymph node metastasis, and poor prognosis together with functional assays on cell migration, invasion, and tumorigenicity are in accordance with the downregulation of miR-335 in gastric cancer. Conclusions Comprehensive evaluation of metastasis and invasion pathway identified a subset of associated genes and confirmed PLAUR and CDH11, both targets of miR-335, to be overexpressed in gastric cancer tissues. DNA methylation of miR-335 may be a promissory strategy for non-invasive approach to gastric cancer. miR-335 (dpeaa)DE-He213 Gastric cancer (dpeaa)DE-He213 Metastasis (dpeaa)DE-He213 PLAUR (dpeaa)DE-He213 CDH11 (dpeaa)DE-He213 Methylation (dpeaa)DE-He213 Polakovicova, Iva aut Carrasco-Véliz, Nicolás aut Lobos-González, Lorena aut Riquelme, Ismael aut Carrasco-Avino, Gonzalo aut Bizama, Carolina aut Norero, Enrique aut Owen, Gareth I. aut Roa, Juan C. aut Corvalán, Alejandro H. aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 9(2017), 1 vom: 17. Okt. (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:9 year:2017 number:1 day:17 month:10 https://dx.doi.org/10.1186/s13148-017-0413-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2017 1 17 10
allfields_unstemmed	10.1186/s13148-017-0413-8 doi (DE-627)SPR03067557X (SPR)s13148-017-0413-8-e DE-627 ger DE-627 rakwb eng Sandoval-Bórquez, Alejandra verfasserin aut MicroRNA-335-5p is a potential suppressor of metastasis and invasion in gastric cancer 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Multiple aberrant microRNA expression has been reported in gastric cancer. Among them, microRNA-335-5p (miR-335), a microRNA regulated by DNA methylation, has been reported to possess both tumor suppressor and tumor promoter activities. Results Herein, we show that miR-335 levels are reduced in gastric cancer and significantly associate with lymph node metastasis, depth of tumor invasion, and ultimately poor patient survival in a cohort of Amerindian/Hispanic patients. In two gastric cancer cell lines AGS and, Hs 746T the exogenous miR-335 decreases migration, invasion, viability, and anchorage-independent cell growth capacities. Performing a PCR array on cells transfected with miR-335, 19 (30.6%) out of 62 genes involved in metastasis and tumor invasion showed decreased transcription levels. Network enrichment analysis narrowed these genes to nine (PLAUR, CDH11, COL4A2, CTGF, CTSK, MMP7, PDGFA, TIMP1, and TIMP2). Elevated levels of PLAUR, a validated target gene, and CDH11 were confirmed in tumors with low expression of miR-335. The 3′UTR of CDH11 was identified to be directly targeted by miR-335. Downregulation of miR-335 was also demonstrated in plasma samples from gastric cancer patients and inversely correlated with DNA methylation of promoter region (Z = 1.96, p = 0.029). DNA methylation, evaluated by methylation-specific PCR assay, was found in plasma from 23 (56.1%) out of 41 gastric cancer patients but in only 9 (30%) out of 30 healthy donors (p = 0.029, Pearson’s correlation). Taken in consideration, our results of the association with depth of invasion, lymph node metastasis, and poor prognosis together with functional assays on cell migration, invasion, and tumorigenicity are in accordance with the downregulation of miR-335 in gastric cancer. Conclusions Comprehensive evaluation of metastasis and invasion pathway identified a subset of associated genes and confirmed PLAUR and CDH11, both targets of miR-335, to be overexpressed in gastric cancer tissues. DNA methylation of miR-335 may be a promissory strategy for non-invasive approach to gastric cancer. miR-335 (dpeaa)DE-He213 Gastric cancer (dpeaa)DE-He213 Metastasis (dpeaa)DE-He213 PLAUR (dpeaa)DE-He213 CDH11 (dpeaa)DE-He213 Methylation (dpeaa)DE-He213 Polakovicova, Iva aut Carrasco-Véliz, Nicolás aut Lobos-González, Lorena aut Riquelme, Ismael aut Carrasco-Avino, Gonzalo aut Bizama, Carolina aut Norero, Enrique aut Owen, Gareth I. aut Roa, Juan C. aut Corvalán, Alejandro H. aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 9(2017), 1 vom: 17. Okt. (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:9 year:2017 number:1 day:17 month:10 https://dx.doi.org/10.1186/s13148-017-0413-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2017 1 17 10
allfieldsGer	10.1186/s13148-017-0413-8 doi (DE-627)SPR03067557X (SPR)s13148-017-0413-8-e DE-627 ger DE-627 rakwb eng Sandoval-Bórquez, Alejandra verfasserin aut MicroRNA-335-5p is a potential suppressor of metastasis and invasion in gastric cancer 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Multiple aberrant microRNA expression has been reported in gastric cancer. Among them, microRNA-335-5p (miR-335), a microRNA regulated by DNA methylation, has been reported to possess both tumor suppressor and tumor promoter activities. Results Herein, we show that miR-335 levels are reduced in gastric cancer and significantly associate with lymph node metastasis, depth of tumor invasion, and ultimately poor patient survival in a cohort of Amerindian/Hispanic patients. In two gastric cancer cell lines AGS and, Hs 746T the exogenous miR-335 decreases migration, invasion, viability, and anchorage-independent cell growth capacities. Performing a PCR array on cells transfected with miR-335, 19 (30.6%) out of 62 genes involved in metastasis and tumor invasion showed decreased transcription levels. Network enrichment analysis narrowed these genes to nine (PLAUR, CDH11, COL4A2, CTGF, CTSK, MMP7, PDGFA, TIMP1, and TIMP2). Elevated levels of PLAUR, a validated target gene, and CDH11 were confirmed in tumors with low expression of miR-335. The 3′UTR of CDH11 was identified to be directly targeted by miR-335. Downregulation of miR-335 was also demonstrated in plasma samples from gastric cancer patients and inversely correlated with DNA methylation of promoter region (Z = 1.96, p = 0.029). DNA methylation, evaluated by methylation-specific PCR assay, was found in plasma from 23 (56.1%) out of 41 gastric cancer patients but in only 9 (30%) out of 30 healthy donors (p = 0.029, Pearson’s correlation). Taken in consideration, our results of the association with depth of invasion, lymph node metastasis, and poor prognosis together with functional assays on cell migration, invasion, and tumorigenicity are in accordance with the downregulation of miR-335 in gastric cancer. Conclusions Comprehensive evaluation of metastasis and invasion pathway identified a subset of associated genes and confirmed PLAUR and CDH11, both targets of miR-335, to be overexpressed in gastric cancer tissues. DNA methylation of miR-335 may be a promissory strategy for non-invasive approach to gastric cancer. miR-335 (dpeaa)DE-He213 Gastric cancer (dpeaa)DE-He213 Metastasis (dpeaa)DE-He213 PLAUR (dpeaa)DE-He213 CDH11 (dpeaa)DE-He213 Methylation (dpeaa)DE-He213 Polakovicova, Iva aut Carrasco-Véliz, Nicolás aut Lobos-González, Lorena aut Riquelme, Ismael aut Carrasco-Avino, Gonzalo aut Bizama, Carolina aut Norero, Enrique aut Owen, Gareth I. aut Roa, Juan C. aut Corvalán, Alejandro H. aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 9(2017), 1 vom: 17. Okt. (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:9 year:2017 number:1 day:17 month:10 https://dx.doi.org/10.1186/s13148-017-0413-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2017 1 17 10
allfieldsSound	10.1186/s13148-017-0413-8 doi (DE-627)SPR03067557X (SPR)s13148-017-0413-8-e DE-627 ger DE-627 rakwb eng Sandoval-Bórquez, Alejandra verfasserin aut MicroRNA-335-5p is a potential suppressor of metastasis and invasion in gastric cancer 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Multiple aberrant microRNA expression has been reported in gastric cancer. Among them, microRNA-335-5p (miR-335), a microRNA regulated by DNA methylation, has been reported to possess both tumor suppressor and tumor promoter activities. Results Herein, we show that miR-335 levels are reduced in gastric cancer and significantly associate with lymph node metastasis, depth of tumor invasion, and ultimately poor patient survival in a cohort of Amerindian/Hispanic patients. In two gastric cancer cell lines AGS and, Hs 746T the exogenous miR-335 decreases migration, invasion, viability, and anchorage-independent cell growth capacities. Performing a PCR array on cells transfected with miR-335, 19 (30.6%) out of 62 genes involved in metastasis and tumor invasion showed decreased transcription levels. Network enrichment analysis narrowed these genes to nine (PLAUR, CDH11, COL4A2, CTGF, CTSK, MMP7, PDGFA, TIMP1, and TIMP2). Elevated levels of PLAUR, a validated target gene, and CDH11 were confirmed in tumors with low expression of miR-335. The 3′UTR of CDH11 was identified to be directly targeted by miR-335. Downregulation of miR-335 was also demonstrated in plasma samples from gastric cancer patients and inversely correlated with DNA methylation of promoter region (Z = 1.96, p = 0.029). DNA methylation, evaluated by methylation-specific PCR assay, was found in plasma from 23 (56.1%) out of 41 gastric cancer patients but in only 9 (30%) out of 30 healthy donors (p = 0.029, Pearson’s correlation). Taken in consideration, our results of the association with depth of invasion, lymph node metastasis, and poor prognosis together with functional assays on cell migration, invasion, and tumorigenicity are in accordance with the downregulation of miR-335 in gastric cancer. Conclusions Comprehensive evaluation of metastasis and invasion pathway identified a subset of associated genes and confirmed PLAUR and CDH11, both targets of miR-335, to be overexpressed in gastric cancer tissues. DNA methylation of miR-335 may be a promissory strategy for non-invasive approach to gastric cancer. miR-335 (dpeaa)DE-He213 Gastric cancer (dpeaa)DE-He213 Metastasis (dpeaa)DE-He213 PLAUR (dpeaa)DE-He213 CDH11 (dpeaa)DE-He213 Methylation (dpeaa)DE-He213 Polakovicova, Iva aut Carrasco-Véliz, Nicolás aut Lobos-González, Lorena aut Riquelme, Ismael aut Carrasco-Avino, Gonzalo aut Bizama, Carolina aut Norero, Enrique aut Owen, Gareth I. aut Roa, Juan C. aut Corvalán, Alejandro H. aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 9(2017), 1 vom: 17. Okt. (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:9 year:2017 number:1 day:17 month:10 https://dx.doi.org/10.1186/s13148-017-0413-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2017 1 17 10
language	English
source	Enthalten in Clinical epigenetics 9(2017), 1 vom: 17. Okt. volume:9 year:2017 number:1 day:17 month:10
sourceStr	Enthalten in Clinical epigenetics 9(2017), 1 vom: 17. Okt. volume:9 year:2017 number:1 day:17 month:10
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	miR-335 Gastric cancer Metastasis PLAUR CDH11 Methylation
isfreeaccess_bool	true
container_title	Clinical epigenetics
authorswithroles_txt_mv	Sandoval-Bórquez, Alejandra @@aut@@ Polakovicova, Iva @@aut@@ Carrasco-Véliz, Nicolás @@aut@@ Lobos-González, Lorena @@aut@@ Riquelme, Ismael @@aut@@ Carrasco-Avino, Gonzalo @@aut@@ Bizama, Carolina @@aut@@ Norero, Enrique @@aut@@ Owen, Gareth I. @@aut@@ Roa, Juan C. @@aut@@ Corvalán, Alejandro H. @@aut@@
publishDateDaySort_date	2017-10-17T00:00:00Z
hierarchy_top_id	626459028
id	SPR03067557X
language_de	englisch
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Among them, microRNA-335-5p (miR-335), a microRNA regulated by DNA methylation, has been reported to possess both tumor suppressor and tumor promoter activities. Results Herein, we show that miR-335 levels are reduced in gastric cancer and significantly associate with lymph node metastasis, depth of tumor invasion, and ultimately poor patient survival in a cohort of Amerindian/Hispanic patients. In two gastric cancer cell lines AGS and, Hs 746T the exogenous miR-335 decreases migration, invasion, viability, and anchorage-independent cell growth capacities. Performing a PCR array on cells transfected with miR-335, 19 (30.6%) out of 62 genes involved in metastasis and tumor invasion showed decreased transcription levels. Network enrichment analysis narrowed these genes to nine (PLAUR, CDH11, COL4A2, CTGF, CTSK, MMP7, PDGFA, TIMP1, and TIMP2). Elevated levels of PLAUR, a validated target gene, and CDH11 were confirmed in tumors with low expression of miR-335. The 3′UTR of CDH11 was identified to be directly targeted by miR-335. Downregulation of miR-335 was also demonstrated in plasma samples from gastric cancer patients and inversely correlated with DNA methylation of promoter region (Z = 1.96, p = 0.029). DNA methylation, evaluated by methylation-specific PCR assay, was found in plasma from 23 (56.1%) out of 41 gastric cancer patients but in only 9 (30%) out of 30 healthy donors (p = 0.029, Pearson’s correlation). Taken in consideration, our results of the association with depth of invasion, lymph node metastasis, and poor prognosis together with functional assays on cell migration, invasion, and tumorigenicity are in accordance with the downregulation of miR-335 in gastric cancer. Conclusions Comprehensive evaluation of metastasis and invasion pathway identified a subset of associated genes and confirmed PLAUR and CDH11, both targets of miR-335, to be overexpressed in gastric cancer tissues. 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author	Sandoval-Bórquez, Alejandra
spellingShingle	Sandoval-Bórquez, Alejandra misc miR-335 misc Gastric cancer misc Metastasis misc PLAUR misc CDH11 misc Methylation MicroRNA-335-5p is a potential suppressor of metastasis and invasion in gastric cancer
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topic_title	MicroRNA-335-5p is a potential suppressor of metastasis and invasion in gastric cancer miR-335 (dpeaa)DE-He213 Gastric cancer (dpeaa)DE-He213 Metastasis (dpeaa)DE-He213 PLAUR (dpeaa)DE-He213 CDH11 (dpeaa)DE-He213 Methylation (dpeaa)DE-He213
topic	misc miR-335 misc Gastric cancer misc Metastasis misc PLAUR misc CDH11 misc Methylation
topic_unstemmed	misc miR-335 misc Gastric cancer misc Metastasis misc PLAUR misc CDH11 misc Methylation
topic_browse	misc miR-335 misc Gastric cancer misc Metastasis misc PLAUR misc CDH11 misc Methylation
format_facet	Elektronische Aufsätze Aufsätze Elektronische Ressource
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title	MicroRNA-335-5p is a potential suppressor of metastasis and invasion in gastric cancer
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title_full	MicroRNA-335-5p is a potential suppressor of metastasis and invasion in gastric cancer
author_sort	Sandoval-Bórquez, Alejandra
journal	Clinical epigenetics
journalStr	Clinical epigenetics
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author_browse	Sandoval-Bórquez, Alejandra Polakovicova, Iva Carrasco-Véliz, Nicolás Lobos-González, Lorena Riquelme, Ismael Carrasco-Avino, Gonzalo Bizama, Carolina Norero, Enrique Owen, Gareth I. Roa, Juan C. Corvalán, Alejandro H.
container_volume	9
format_se	Elektronische Aufsätze
author-letter	Sandoval-Bórquez, Alejandra
doi_str_mv	10.1186/s13148-017-0413-8
title_sort	microrna-335-5p is a potential suppressor of metastasis and invasion in gastric cancer
title_auth	MicroRNA-335-5p is a potential suppressor of metastasis and invasion in gastric cancer
abstract	Background Multiple aberrant microRNA expression has been reported in gastric cancer. Among them, microRNA-335-5p (miR-335), a microRNA regulated by DNA methylation, has been reported to possess both tumor suppressor and tumor promoter activities. Results Herein, we show that miR-335 levels are reduced in gastric cancer and significantly associate with lymph node metastasis, depth of tumor invasion, and ultimately poor patient survival in a cohort of Amerindian/Hispanic patients. In two gastric cancer cell lines AGS and, Hs 746T the exogenous miR-335 decreases migration, invasion, viability, and anchorage-independent cell growth capacities. Performing a PCR array on cells transfected with miR-335, 19 (30.6%) out of 62 genes involved in metastasis and tumor invasion showed decreased transcription levels. Network enrichment analysis narrowed these genes to nine (PLAUR, CDH11, COL4A2, CTGF, CTSK, MMP7, PDGFA, TIMP1, and TIMP2). Elevated levels of PLAUR, a validated target gene, and CDH11 were confirmed in tumors with low expression of miR-335. The 3′UTR of CDH11 was identified to be directly targeted by miR-335. Downregulation of miR-335 was also demonstrated in plasma samples from gastric cancer patients and inversely correlated with DNA methylation of promoter region (Z = 1.96, p = 0.029). DNA methylation, evaluated by methylation-specific PCR assay, was found in plasma from 23 (56.1%) out of 41 gastric cancer patients but in only 9 (30%) out of 30 healthy donors (p = 0.029, Pearson’s correlation). Taken in consideration, our results of the association with depth of invasion, lymph node metastasis, and poor prognosis together with functional assays on cell migration, invasion, and tumorigenicity are in accordance with the downregulation of miR-335 in gastric cancer. Conclusions Comprehensive evaluation of metastasis and invasion pathway identified a subset of associated genes and confirmed PLAUR and CDH11, both targets of miR-335, to be overexpressed in gastric cancer tissues. DNA methylation of miR-335 may be a promissory strategy for non-invasive approach to gastric cancer. © The Author(s). 2017
abstractGer	Background Multiple aberrant microRNA expression has been reported in gastric cancer. Among them, microRNA-335-5p (miR-335), a microRNA regulated by DNA methylation, has been reported to possess both tumor suppressor and tumor promoter activities. Results Herein, we show that miR-335 levels are reduced in gastric cancer and significantly associate with lymph node metastasis, depth of tumor invasion, and ultimately poor patient survival in a cohort of Amerindian/Hispanic patients. In two gastric cancer cell lines AGS and, Hs 746T the exogenous miR-335 decreases migration, invasion, viability, and anchorage-independent cell growth capacities. Performing a PCR array on cells transfected with miR-335, 19 (30.6%) out of 62 genes involved in metastasis and tumor invasion showed decreased transcription levels. Network enrichment analysis narrowed these genes to nine (PLAUR, CDH11, COL4A2, CTGF, CTSK, MMP7, PDGFA, TIMP1, and TIMP2). Elevated levels of PLAUR, a validated target gene, and CDH11 were confirmed in tumors with low expression of miR-335. The 3′UTR of CDH11 was identified to be directly targeted by miR-335. Downregulation of miR-335 was also demonstrated in plasma samples from gastric cancer patients and inversely correlated with DNA methylation of promoter region (Z = 1.96, p = 0.029). DNA methylation, evaluated by methylation-specific PCR assay, was found in plasma from 23 (56.1%) out of 41 gastric cancer patients but in only 9 (30%) out of 30 healthy donors (p = 0.029, Pearson’s correlation). Taken in consideration, our results of the association with depth of invasion, lymph node metastasis, and poor prognosis together with functional assays on cell migration, invasion, and tumorigenicity are in accordance with the downregulation of miR-335 in gastric cancer. Conclusions Comprehensive evaluation of metastasis and invasion pathway identified a subset of associated genes and confirmed PLAUR and CDH11, both targets of miR-335, to be overexpressed in gastric cancer tissues. DNA methylation of miR-335 may be a promissory strategy for non-invasive approach to gastric cancer. © The Author(s). 2017
abstract_unstemmed	Background Multiple aberrant microRNA expression has been reported in gastric cancer. Among them, microRNA-335-5p (miR-335), a microRNA regulated by DNA methylation, has been reported to possess both tumor suppressor and tumor promoter activities. Results Herein, we show that miR-335 levels are reduced in gastric cancer and significantly associate with lymph node metastasis, depth of tumor invasion, and ultimately poor patient survival in a cohort of Amerindian/Hispanic patients. In two gastric cancer cell lines AGS and, Hs 746T the exogenous miR-335 decreases migration, invasion, viability, and anchorage-independent cell growth capacities. Performing a PCR array on cells transfected with miR-335, 19 (30.6%) out of 62 genes involved in metastasis and tumor invasion showed decreased transcription levels. Network enrichment analysis narrowed these genes to nine (PLAUR, CDH11, COL4A2, CTGF, CTSK, MMP7, PDGFA, TIMP1, and TIMP2). Elevated levels of PLAUR, a validated target gene, and CDH11 were confirmed in tumors with low expression of miR-335. The 3′UTR of CDH11 was identified to be directly targeted by miR-335. Downregulation of miR-335 was also demonstrated in plasma samples from gastric cancer patients and inversely correlated with DNA methylation of promoter region (Z = 1.96, p = 0.029). DNA methylation, evaluated by methylation-specific PCR assay, was found in plasma from 23 (56.1%) out of 41 gastric cancer patients but in only 9 (30%) out of 30 healthy donors (p = 0.029, Pearson’s correlation). Taken in consideration, our results of the association with depth of invasion, lymph node metastasis, and poor prognosis together with functional assays on cell migration, invasion, and tumorigenicity are in accordance with the downregulation of miR-335 in gastric cancer. Conclusions Comprehensive evaluation of metastasis and invasion pathway identified a subset of associated genes and confirmed PLAUR and CDH11, both targets of miR-335, to be overexpressed in gastric cancer tissues. DNA methylation of miR-335 may be a promissory strategy for non-invasive approach to gastric cancer. © The Author(s). 2017
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title_short	MicroRNA-335-5p is a potential suppressor of metastasis and invasion in gastric cancer
url	https://dx.doi.org/10.1186/s13148-017-0413-8
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author2	Polakovicova, Iva Carrasco-Véliz, Nicolás Lobos-González, Lorena Riquelme, Ismael Carrasco-Avino, Gonzalo Bizama, Carolina Norero, Enrique Owen, Gareth I. Roa, Juan C. Corvalán, Alejandro H.
author2Str	Polakovicova, Iva Carrasco-Véliz, Nicolás Lobos-González, Lorena Riquelme, Ismael Carrasco-Avino, Gonzalo Bizama, Carolina Norero, Enrique Owen, Gareth I. Roa, Juan C. Corvalán, Alejandro H.
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up_date	2024-07-03T19:29:20.003Z
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