MicroRNAs (miRNA/miRs) are small, non-coding RNA molecules (19-25 nucleotides in length), which function to regulate gene expression. It has been reported that miR-128 serves an important role in regulating cancer cell growth; increasing evidence has indicated that the expression of miR-128 is decreased in pancreatic cancer (PC) cells. However, the specific mechanisms of miR-128 in regulating PC cell growth are unclear. In the present study, it was confirmed that the expression of miR-128 was significantly decreased within PC tissues compared with adjacent normal tissues via reverse transcription-quantitative polymerase chain reaction analysis. In addition, miR-128 mimics inhibited PC MIA-PaCa2 cell growth by enhancing cell apoptosis in a caspase-dependent manner. Furthermore, the results of the present study demonstrated that double minute 4 (MDM4) may be a direct target for miR-128 via a dual luciferase report assay; miR-128 may inhibit MDM4 expression, and increase p53 and cleaved caspase-3 protein expression levels. In summary, the present study indicated that miR-128 is downregulated in PC, and it may be a promising target for future PC diagnosis and treatment.
PurposeThis paper studied the effect of TMEFF2 expression on pancreatic cancer and its mechanism.MethodsA total of 72 pancreatic cancer patients were enrolled. AsPC1 and Panc1 cells were transfected. SB203580 was used to treat AsPC1 cells. CCK8 assay, colony formation analysis, Transwell experiment and Tunel test were performed. In vivo studies in nude mice were conducted. Immunohistochemistry, qRT-PCR and Western blot were used to detect genes expression.ResultsTMEFF2 was downregulated in pancreatic cancer tissues and cells (P<0.001). Low TMEFF2 expression was associated with larger tumor size and advanced stage and poor differentiation (P<0.01). Compared with the NC group, AsPC1 and Panc1 cells of the TMEFF2 group exhibited much lower OD450 values, colony number, tumor volume and weight, migration and invasion cell numbers, obviously higher E-cadherin protein expression, lower Snail, Vimentin, MMP-2 and MMP-9 proteins expression, lower phosphorylation level of MAPK signaling pathway, and more apoptotic cells. AsPC1 cells of the SB203580 group showed much lower OD450 value when compared with the siTMEFF2 group. Significantly decreased colony number, migration and invasion number, higher E-cadherin protein expression and lower Snail, Vimentin, MMP-2 and MMP-9 proteins expression were found in AsPC1 cells of the siTMEFF2+ SB203580 group when compared with the siTMEFF2+ DMSO group.ConclusionTMEFF2 inhibits pancreatic cancer cells proliferation, migration, and invasion by suppressing the phosphorylation of the MAPK signaling pathway.
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