MiR-129-5p functions as a tumor suppressor in gastric cancer progression through targeting ADAM9.

MicroRNAs (miRNAs) are identified as key regulators in cancer initiation, progression and metastasis including gastric cancer (GC). The aim of the study is to explore clinical significance and potential mechanism of miR-129-5p in GC development. In the study, our results found that miR-129-5p expression was significantly downregulated in GC tissues, compared with adjacent normal tissues using qRT-PCR analyses. Furthermore, lower miR-129-5p expression closely associated with tumor size and lymph node invasion and poor prognosis of GC patients. Using CCK8 assay, cell colony formation, transwell invasion assay, we demonstrated that miR-129-5p overexpression reduced cell proliferation, cell colony formation and cell invasion capacity in MKN45 (higher miR-129-5p expression) and SGC-7901 (lower miR-129-5p expression). However, downregulation of miR-129-5p had reverse effects on cell proliferation and invasion. Targeting association analysis, dual luciferase assay, qRT-PCR and western blot analysis results verified that miR-129-5p could target the 3'UTR of ADAM9 mRNA and regulated its protein expression. Furthermore, we confirmed that miR-129-5p suppressed cell proliferation and invasion ability through regulating ADAM9. In vivo, upregulation of miR-129-5p also inhibited tumor growth. Therefore, these results indicated that miR-129-5p functioned as a tumor suppressor in GC and may be a potential target of GC treatment.

Liu Q ，Jiang J ，Fu Y ，Liu T ，Yu Y ，Zhang X ... -  《-》

MiR-374b-5p suppresses RECK expression and promotes gastric cancer cell invasion and metastasis.

Xie J ，Tan ZH ，Tang X ，Mo MS ，Liu YP ，Gan RL ，Li Y ，Zhang L ，Li GQ ... -  《-》

ADAM9 functions as a promoter of gastric cancer growth which is negatively and post-transcriptionally regulated by miR-126.

Wang J ，Zhou Y ，Fei X ，Chen X ，Yan J ，Liu B ，Zhu Z ... -  《-》

miR-509-3-5P inhibits the invasion and lymphatic metastasis by targeting PODXL and serves as a novel prognostic indicator for gastric cancer.

Zhang J ，Zhu Z ，Sheng J ，Yu Z ，Yao B ，Huang K ，Zhou L ，Qiu Z ，Huang C ... -  《Oncotarget》

MicroRNA-148a suppresses tumor cell invasion and metastasis by downregulating ROCK1 in gastric cancer.

MicroRNAs (miRNA) have been documented playing a critical role in cancer development and progression. In this study, we investigate the role of miR-148a in gastric cancer metastasis. We examined miR-148a levels in 90 gastric cancer samples by qRT-PCR and analyzed the clinicopathologic significance of miR-148a expression. The gastric cancer cells stably expressing miRNA-148a were analyzed for migration and invasion assays in vitro and metastasis assays in vivo; the target genes of miR-148a were further explored. We found that miR-148a expression was suppressed by more than 4-fold in gastric cancer compared with their corresponding nontumorous tissues, and the downregulated miR-148a was significantly associated with tumor-node-metastasis (TNM) stage and lymph node-metastasis. Functional assays showed that overexpression of miR-148a suppressed gastric cancer cell migration and invasion in vitro and lung metastasis formation in vivo. In addition, overexpression of miR-148a in GC cells could reduce the mRNA and protein levels of ROCK1, whereas miR-148a silencing significantly increased ROCK1 expression. Luciferase assays confirmed that miR-148a could directly bind to the 2 sites of 3' untranslated region of ROCK1. Moreover, in gastric cancer tissues, we observed an inverse correlation between miR-148a and ROCK1 expression. Knockdown of ROCK1 significantly inhibited gastric cancer cell migration and invasion resembling that of miR-148a overexpression. We further found that ROCK1 was involved in miR-148a-induced suppression of gastric cancer cell migration and invasion. miR-148a functions as a tumor metastasis suppressor in gastric cancer, and downregulation of miR-148a contributes to gastric cancer lymph node-metastasis and progression. miR-148a may have a therapeutic potential to suppress gastric cancer metastasis.

Zheng B ，Liang L ，Wang C ，Huang S ，Cao X ，Zha R ，Liu L ，Jia D ，Tian Q ，Wu J ，Ye Y ，Wang Q ，Long Z ，Zhou Y ，Du C ，He X ，Shi Y ... -  《-》