miR‑146b‑5p promotes colorectal cancer progression by targeting TRAF6

Abstract

Increasing evidence highlights the multiple roles of microRNAs (miRs) in the tumorigenesis of colorectal cancer (CRC); however, the molecular mechanism, particularly the target of miR-146b-5p in CRC has not been fully elucidated. The present study aimed to elucidate the influence of miR-146b-5p via regulating tumor necrosis factor receptor-associated factor 6 (TRAF6) in CRC. The expression levels of miR-146b-5p and TRAF6 in CRC tissue and cells were determined by reverse transcription quantitative PCR and western blotting. Binding between miR-146b-5p and TRAF6 was examined using a dual luciferase reporter gene assay. The impact of miR-146b-5p and TRAF6 on proliferation and migration of CRC cells was determined using Cell Counting Kit-8 and Transwell assays, respectively. An animal model of CRC was established to determine the carcinogenic effect of the miR-146b-5p-TRAF6 axis. The results demonstrated that miR-146b-5p was highly expressed in CRC tissue samples compared with in normal adjacent tissue samples and in CRC cells compared with in the normal NCM460 cell line, whereas TRAF6 was expressed at low levels. Overexpression of miR-146b-5p decreased TRAF6 expression in CRC HT29 and SW620 cells. miR-146b-5p targeted and inhibited TRAF6 expression in CRC cells. Furthermore, transfection with a miR-146b-5p mimic promoted the proliferation, migration and invasion of CRC cells and tumor growth; however, these effects were abolished by TRAF6 overexpression. Transfection with a miR-146b-5p inhibitor suppressed the proliferation of CRC cells. Taken together, the results from the present study demonstrated that miR-146b-5p could enhance the initiation and tumorigenesis of CRC by targeting TRAF6. These results will help elucidate the mechanisms underlying CRC development and will facilitate the development of targeted therapy for CRC.

Anti-cancer effect of hUC-MSC-derived exosome-mediated delivery of PMO-miR-146b-5p in colorectal cancer

“…was observed in previous study [19][20][21], but whether ePPMO-146b exerted equal or even stronger effects remained unclear.…”

“…Recently, some miRNA drugs have been approved to enter clinical trials on indications other than solid tumors, such as cutaneous T-cell lymphoma and Alport syndrome [37,38]. Many data have demonstrated a de nitive protumorigenic role of miR-146b in CRC, suggesting that ASO-miR-146b is feasible for developing a targeted drug [19][20][21]. To overcome the poor cellular uptake of oligonucleotide drugs, nanotechnology has been developed for miRNA or ASO delivery.…”

“…We previously reported that miR-146b-5p (miR-146b) signi cantly promoted EMT phenotypes through Smad4 in CRC cells [19]. An in vivo study has demonstrated that miR-146b may play a tumor-promoting role in establishment of colorectal tumor [20,21]. To therapeutically modulate miR-146b expression, we employed a synthetic anti-miR-146b ASO (PMO-146b) that are complementary to the mature miR-146b.…”

Anticancer effect of hUC-MSC-derived exosome-mediated delivery of PMO-miR-146b-5p in colorectal cancer

“…We previously reported that miR-146b-5p (miR-146b) significantly promoted epithelial–mesenchymal transition phenotypes through Smad4 in CRC cells [ 19 ]. An in vivo study has demonstrated that miR-146b may play a tumor-promoting role in establishment of CRC [ 20 , 21 ]. To therapeutically modulate miR-146b expression, we employed a synthetic anti-miR-146b ASO (PMO-146b) that is complementary to the mature miR-146b.…”

MiR-146b-5p/SEMA3G regulates epithelial-mesenchymal transition in clear cell renal cell carcinoma

“…MiR-146b-5p can play a pro-cancer or anti-cancer role in cancer progression. Shi et al [9] showed that miR-146b-5p could promote colorectal cancer development through targeting TRAF6. Ren et al [10] disclosed that miR-146b-5p is a cholangiocarcinoma inhibitor through targeting TRAF6 to repress proliferation and stimulate apoptosis of cholangiocarcinoma cells.…”