We had earlier shown that the microRNA-143 (miR-143) replenishment not only chemosensitizers CRC cell line with mutant KRAS instead of wild-type KRAS gene, to paclitaxel-mediated cytotoxicity, but also inhibits cell migration and invasion ability.
We extracted and estimated the hazard ratios for survival outcomes, which compared low and high expression levels of miR-143/145 in colorectal cancer patients in the available studies.
We found a global dysregulation of miRNAs, including an oncogenic miR-17-92 cluster and oncosuppressive miR-143-145 cluster, and snoRNAs in synchronous CRC.
In vitro functional studies indicated that miR-143 and miR-145 appear to function in opposing manners to either inhibit or augment cell proliferation in a metastatic CRC model.
Following overexpression of miR-143 in CRC cells, target gene matrix metalloproteinase 7 (MMP7) expression was detected by quantitative real-time PCR (qRT-PCR) and western blot.
These results indicate that miR-143-3p acts as an anti-oncogene by downregulating ITGA6/ASAP3 protein expression and could offer new insight into potential therapeutic targets for CRC.
We found that 67 miRNA precursors are upregulated in rectal cancer (p<0.05) and 21 of those have never been reported in colorectal cancer (CRC); 39 miRNA precursors are downregulated (p<0.05) and 24 novel dysregulated miRNAs were identified in rectal cancer. miR-31, miR-126 and miR-143 are differentially expressed between colon cancer and rectal cancer.
Bioinformatics analysis, dual-luciferase reporter assays, and RNA immunoprecipitation assays showed that miR-143 can interact with UCC, and we found that UCC expression inversely correlates with miR-143 expression in CRC specimens.
In order to evaluate if miR-143 and/or let-7b replenishment would re-sensitize CRC cells to paclitaxel treatment, we investigated in effect of miR-143 and let-7b replenishments on sensitivity to paclitaxel treatment in KRAS mutant LoVo and wild-type SW48 CRC cell lines.
The downregulation of miR-143 was further evaluated in colon cancer cell lines and in paired CRC and adjacent non-cancerous colonic tissues by qRT-PCR.
MiR-20a and miR-31 were found to be significantly upregulated in more than one study, and miR-143 and miR-145 were found to be significantly downregulated in CRC tissue in six or more studies.
Taken together, these results revealed that miR-143 levels in human blood and tumor tissues are associated with CRC cancer occurrence, metastasis and drug resistance, and miR-143 levels may be used as a new diagnostic marker and therapeutic target for CRC in the future.
There was a higher expression of miR-21 and lower expression of miR-143 in CRC tissue in comparison with adjacent normal colon tissue (P < 0.0001; P < 0.0001, respectively).
According to our results, miR-21, a miRNA that is up-regulated in CRC, and miR-143, a miRNA that is down-regulated in CRC, are the two miRNAs that dominated the miRNA population in CR tissues, and probably are also the most important miRNAs in CRCs.