title: Overexpression of paxillin induced by miR-137 suppression promotes tumor progression and metastasis in colorectal cancer.
abstract: The deregulation of paxillin (PXN) has been involved in the progression and metastasis of different malignancies including colorectal cancer (CRC). miR-137 is frequently suppressed in CRC. PXN is predicted to be a direct target of miR-137 in CRC cells. On this basis, we hypothesized that overexpression of PXN induced by suppression of miR-137 may promote tumor progression and metastasis and predicts poor prognosis. We detected the expression of PXN and miR-137 in clinical tumor tissues by immunohistochemical analysis and real-time PCR, positive PXN staining was observed in 198 of the 247 (80.1%) cases, whereas no or weak PXN staining was observed in the adjacent non-cancerous area. Higher level of PXN messenger RNA (mRNA) and lower level of miR-137 was observed in cancer tissues than adjacent non-cancerous tissues. High expression of PXN and low expression of miR-137 was associated with aggressive tumor phenotype and adverse prognosis. Moreover, the expression of PXN was negatively correlated with miR-137 expression. A dual-luciferase reporter gene assay validated that PXN was a direct target of miR-137. The use of miR-137 mimics or inhibitor could decrease or increase PXN mRNA and protein levels in CRC cell lines. Knockdown of PXN or ectopic expression of miR-137 could markedly inhibit cell proliferation, migration and invasion in vitro and repress tumor growth and metastasis in vivo. Taken together, these results demonstrated that overexpression of PXN induced by suppression of miR-137 promotes tumor progression and metastasis and could serve as an independent prognostic indicator in CRC patients.
authors.affiliation: State Key Laboratory of Oncology in South China.
authors.forename: Dong-Liang
authors.initials: DL
authors.lastname: Chen
authors.forename: De-Shen
authors.initials: DS
authors.lastname: Wang
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Wu
authors.forename: Zhao-Lei
authors.initials: ZL
authors.lastname: Zeng
authors.forename: Hui-Yan
authors.initials: HY
authors.lastname: Luo
authors.forename: Miao-Zhen
authors.initials: MZ
authors.lastname: Qiu
authors.forename: Chao
authors.initials: C
authors.lastname: Ren
authors.forename: Dong-Sheng
authors.initials: DS
authors.lastname: Zhang
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Wang
authors.forename: Feng-Hua
authors.initials: FH
authors.lastname: Wang
authors.forename: Yu-Hong
authors.initials: YH
authors.lastname: Li
authors.forename: Tie-Bang
authors.initials: TB
authors.lastname: Kang
authors.forename: Rui-Hua
authors.initials: RH
authors.lastname: Xu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D009368:Neoplasm Transplantation; D051419:Paxillin / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D014183:Transplantation, Heterologous
chemical_list: C545567:MIRN137 microRNA, human; D035683:MicroRNAs; D051419:Paxillin; D012333:RNA, Messenger; D034741:RNA, Small Interfering