Colorectal cancer (CRC) is a major cause of cancer-related deaths worldwide. miR-34 induces changes of its downstream genes and plays a key role in altering the apoptotic cycle and pathways of downstream cells and therefore influences carcinogenesis.
We observed significantly greater expression of <i>TLR4</i>, <i>IL1B</i>, <i>IL8</i>, and miR-135b in CRA lesions and <i>TLR2</i>, <i>IL1B</i>, <i>IL6</i>, <i>IL8</i>, miR-34a and miR-135b in CRC tumours compared to their respective normal tissues.
miR-34a might function as a predictor of fluorouracil chemosensitivity in CRC, and a combination strategy of miR-34a with fluorouracil was expected to be more beneficial for CRC patients.
The CRC-related SNHG7 and miR-34a might be implicated in CRC progression via GALNT7, suggesting the potential usage of SNHG7/miR-34a/GALNT7 axis in CRC treatment.
The results showed that the expression of miR-34a was downregulated whereas TGF-β1 and VEGF were upregulated in CRC tumor tissues and peripheral blood macrophages.
We found SAMe and MTA raised miR-34a/b expression in CRC cell lines, inhibited migration and invasion <i>in vitro</i> and liver metastasis <i>in vivo</i>.
Expression levels of Smad4 and miR-34a in CRC patients had a significant inverse correlation and overexpressing miR-34a inhibited macroautophagy activation by directly targeting Smad4 through the TGF-β/Smad4 pathway.
We analyzed data on human colorectal carcinomas from the Cancer Genome Atlas collection to determine whether expression of PPP1R11 was affected by altered level or activity of p53, markers of epithelial-to-mesenchymal transition (EMT), or MIR34A or was associated with metastasis.
At the same time, 332 DEGs (188 upregulated and 144 downregulated) were screened out between miR-34a transformed CRC and miR-34a non-transfected CRC samples and they were enriched in 20 GO terms and eight KEGG pathways.
In addition, genes encoding miRNA important for epithelial mesenchymal transition and other metastasis-related effects, such as mir-9, miR-34 and miR-210 can be good candidates for associating their DNA methylation profiles with CRC metastasis.
We previously reported that IL-6R, STAT3 and miR-34a form a positive feedback-loop, which promotes epithelial to mesenchymal transition (EMT), invasion, and metastasis of colorectal cancer (CRC) [1].
Our study suggests that miR-34a is an important tumor suppressor of CRC progression by targeting FMNL2 and E2F5, thus providing new insight into the molecular mechanisms underlying CRC progression and establishing a strong potential for the application of miR-34a as a novel therapeutic marker against CRC.
Moreover, the expression of miR-34a-5p was an independent prognostic factor for CRC recurrence by multivariate analysis (P<0.001 for cohort I, P=0.007 for cohort II).