BackgroundColorectal cancer (CRC) is the most common digestive system malignancy. The molecular events involved in the development and progression of CRC remain unclear. Recently, more and more evidences have showed that deregulated miRNAs participate in colorectal carcinogenesis.MethodsThe expression levels of miR-138 were first examined in CRC cell lines and tumor tissues by real-time PCR. The in vitro and in vivo functional effects of miR-138 were examined further. Luciferase reporter assays were conducted to confirm the targeting associations. Kaplan-Meier analysis and log-rank tests were performed to estimate the overall survival and disease free survival rate.ResultsmiR-138 was found to be down-regulated in human colorectal cancer tissues and cell lines. Ectopic expression of miR-138 resulted in a dramatic inhibition of CRC migration and invasion in vitro and in vivo. Twist basic helix-loop-helix transcription factor 2 gene (TWIST2) was identified as one of the functional target. Restoration of miR-138 resulted in a dramatic reduction of the expression of TWIST2 at both mRNA and protein levels by directly targeting its 3′-untranslated region (3′UTR). Up-regulation of TWIST2 was detected in CRC tumors compared with adjacent normal tissues (P < 0.001) and is inversely correlated with miR-138 expression. We also identified that down-regulation of miR-138 was associated with lymph node metastasis, distant metastasis, and always predicted poor prognosis.ConclusionThese data highlight a pivotal role for miR-138 in the regulation of CRC metastasis by targeting TWIST2, and suggest a potential application of miR-138 in prognosis prediction and CRC treatment.
ZEB2 expression is closely associated with the clinicopathological parameters of gastric cancer. ZEB2 promotes gastric cancer cell migration and invasion at least partly via the regulation of epithelial-mesenchymal transition. ZEB2 is a potential target for gene therapy of aggressive gastric cancer.
Colorectal cancer (CRC) is the third most common cancer type and the fourth leading cause of cancer‑associated mortality worldwide. MicroRNA (miR)‑1246 is involved in differentiation, invasion, metastasis and chemoresistance of certain types of tumor cells. CCNG2 encodes an unconventional cyclin homolog, cyclin G2 (CycG2), associated with growth inhibition, which correlated significantly with lymph node metastasis, clinical stage, histological grade and poor overall survival in numerous cancer types. To investigate the regulation of miR‑1246 on CycG2 expression, and their effects on proliferation and metastasis of CRC, HCT‑116 and LOVO cells were transfected with pre‑miR‑1246 anti‑miR‑1246 and their negative controls. It was demonstrated that the expression of miR‑1246 was significantly increased in CRC tissues and cell lines, which was the opposite of CycG2. miR‑1246 negatively regulated the expression of CycG2 in HCT‑116 and LOVO CRC cells. CCNG2 is a direct target of miR‑1246 in CRC cells. Overexpression of miR‑1246 induced cell proliferation, migration and invasion, while knockdown of miR‑1246 inhibited proliferation, migration and invasion in the CRC cells. Upregulation of miR‑1246 mediated the malignant progression of CRC and is partly attributed to the downregulation of the expression of CycG2. Consequently, these findings provided a molecular basis for the role of miR‑1246/CCNG2 in the progression of human CRC and suggested a novel target for the treatment of CRC.
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