MicroRNA-25 promotes gastric cancer migration, invasion and proliferation by directly targeting transducer of ERBB2, 1 and correlates with poor survival

Abstract

Gastric cancer (GC) is one of the most common tumors and the molecular mechanism underlying its metastasis is still largely unclear. Here, we show that miR-25 was overexpressed in plasma and primary tumor tissues of GC patients with tumor node metastasis stage (III or IV) or lymph node metastasis. MiR-25 inhibition significantly decreased the metastasis, invasion and proliferation of GC cells in vitro, and reduced their capacity to develop distal pulmonary metastases and peritoneal dissemination in vivo. Furthermore, miR-25 repressed transducer of ERBB2, 1 (TOB1) expression by directly binding to TOB1-3'-UTR, and the inverse correlation was observed between the expressions of miR-25 and TOB1 mRNA in primary GC tissues. Moreover, the loss of TOB1 increased the metastasis, invasion and proliferation of GC cells, and the restoration of TOB1 led to suppressed metastasis, invasion and proliferation. The receiver operating characteristics analysis yielded an area under the curve value of 0.7325 in distinguishing the GC patients with death from those with survival. The analysis of optimal cutoff value revealed poor survival in GC patients with high plasma concentrations of miR-25 (>0.2333 amol/μl). Taken together, miR-25 promotes GC progression by directly downregulating TOB1 expression, and may be a noninvasive biomarker for the prognosis of GC patients.

miR-25 promotes glioblastoma cell proliferation and invasion by directly targeting NEFL

“…Down-regulation of NEFL could significantly attenuate the inhibitory effects of knockdown miR-25 on the proliferation, migration, and invasion of U251 cells via activation of the mTOR pathway. LATS2 and ERBB2 were also the direct targets of miR-25 [17,18,34]. LATS2 is a tumor suppressor gene of gastric adenocarcinoma (GAC) [34], malignant mesothelioma [35], ovarian cancer [18], breast cancer [36], non-small cell lung cancer [37], and prostate cancer [36].…”

“…Due to their small size and influence in a broad range of biological processes, miRNAs are very attractive therapeutic targets for GBM. miR-25 is one of the most overexpressed miRNAs in a number of profiling experiments designed for the detection of miRNAs dysregulated in human cancers [16][17][18][19][20][21][22][23][24][25]29]. Li et al reported that miR-25 promoted gastric cancer migration, invasion, and proliferation by directly targeting transducer of ERBB2 and 1 and correlated with poor survival [17].…”

“…[16][17][18][19][20][21][22][23][24][25]. However, the role of miR-25 in glioblastoma tumorigenesis and the underlying molecular mechanisms by which miR-25 exerts its functions had remained-until recently-largely unknown.…”

Mechanisms of peritoneal dissemination in gastric cancer (Review)

“…An increasing number of studies have demonstrated that miRNAs are associated with tumour development and progression (83,84). Certain miRNAs have been established to be associated with peritoneal dissemination in gastric cancer (85)(86)(87). Zheng et al (85) reported that microRNA (miR)-409-3p inhibited the ability of gastric cancer cells to invade and metastasise via targeting radixin.…”

“…Another previous study demonstrated that miR-495 and miR-551a suppressed gastric cancer cell migration and invasion by targeting PRL-3, which exhibits significantly increased expression levels in primary gastric cancer cells with peritoneal dissemination (86). miR-25 was identified to enhance gastric cancer progression by targeting Erb-B2 receptor tyrosine kinase 2 both in vitro and in vivo (87). Other miRNAs have been reported to correlate with peritoneal dissemination in gastric cancer, including miR-200b (88), miR-125a-3q (89) and let-7 miRNAs (90).…”