miR-145-5p restrained cell growth, invasion, migration and tumorigenesis via modulating RHBDD1 in colorectal cancer via the EGFR-associated signaling pathway.

miR-145-5p has been reported to be downregulated and described functioning as a tumor suppressive gene in colorectal cancer (CRC), yet its detailed regulatory function and mechanism in malignant progression of the disease have not been thoroughly understood. In our study, miR-145-5p and rhomboid domain containing 1 (RHBDD1) in CRC tissues and cells were examined by qRT-PCR and western blot. MTT, colony formation, wound healing, Transwell invasion, and flow cytometry assays were performed to evaluate the malignant phenotypes of CRC cells. Xenograft tumor, qRT-PCR, and western blot assays were applied to validate the roles and mechanism of miR-145-5p in CRC in vivo. The interaction between miR-145-5p and RHBDD1 was investigated by luciferase reporter assay and western blot. The changes of the EGFR/Raf/MEK/ERK pathway were detected by western blot. We found miR-145-5p was lowly expressed and low miR-145-5p predicted poor prognosis in CRC, while RHBDD1 was greatly enhanced in CRC cells and tissues. RHBDD1 silencing resulted in inhibiting cell proliferative, invasive, and migratory potentials as well as elevating apoptotic ones in CRC cells. miR-145-5p was inversely related with RHBDD1 expression in CRC tissues. miR-145-5p was found to directly bind to RHBDD1 and restrained its expression in CRC cells. miR-145-5p overexpression repressed CRC cell proliferation, invasion, migration and induced apoptosis, and these effects were reversed by RHBDD1 upregulation. Moreover, in CRC xenograft tumor, its growth was impeded by miR-145-5p via suppressing RHBDD1. Furthermore, miR-145-5p inhibited the expression of EGFR, p-MEK1/2 and p-ERK1/2, in vitro and in vivo by targeting RHBDD1. In conclusion, our study revealed that miR-145-5p overexpression inhibited tumorigenesis in CRC by downregulating RHBDD1 via suppressing the EGFR-associated signaling pathway (EGFR/Raf/MEK/ERK cascades).

Niu Y ，Zhang J ，Tong Y ，Li J ，Liu B ... -  《-》

MicroRNA-138-5p inhibits cell migration, invasion and EMT in breast cancer by directly targeting RHBDD1.

Zhao C ，Ling X ，Li X ，Hou X ，Zhao D ... -  《-》

MiR-346-5p promotes colorectal cancer cell proliferation in vitro and in vivo by targeting FBXL2 and activating the β-catenin signaling pathway.

MiR-346-5p is overexpressed in several cancers, including colorectal cancer (CRC). However, the effects of miR-346-5p on CRC progression have not yet been clarified. In our study, miR-346-5p levels in four CRC cell lines and normal human colon epithelial cells were determined by real-time PCR. SW620 and HCT116 cells were selected and then transfected with miR-346-5p mimic, miR-346-5p inhibitor, or specific siRNAs targeting F-box/LRR-repeat protein 2 (FBXL2). Cell proliferation, cell cycle distribution and cell cycle regulators were examined by CCK-8 assay, flow cytometry, and western blot. The binding of miR-346-5p on 3' untranslated region (UTR) of FBXL2 were verified by dual-luciferase reporter assay. CRC cells were co-transfected with miR-346-5p inhibitor and siFBXL2 to investigate the involvement of FBXL2. Interaction of FBXL2 with forkhead box M1 (FoxM1) was examined by co-immunoprecipitation (Co-IP) assay. The effect of miR-346-5p knockdown on CRC tumorigenesis in vivo was investigated. Here, we found that miR-346-5p overexpression promoted, while miR-346-5p knockdown inhibited cell proliferation and G1-S transition. Inhibition of FBXL2 showed similar effects as miR-346-5p overexpression. Moreover, we verified that FBXL2 was a direct target of miR-346-5p. FBXL2 interacted with FoxM1, and then negatively regulated both FoxM1 and nuclear β-catenin levels. Additionally, FBXL2 knockdown reversed the effects of miR-346-5p inhibitor. In xenograft models, miR-346-5p knockdown significantly inhibited tumor growth, increased FBXL2 expression, and downregulated the levels of FoxM1 and nuclear β-catenin. In conclusion, miR-346-5p may promote CRC growth by targeting FBXL2 and activating the β-catenin signaling pathway. MiR-346-5p may be a novel target in cancer therapy.

Pan S ，Wu W ，Ren F ，Li L ，Li Y ，Li W ，Wang A ，Liu D ，Dong Y ... -  《-》

MiR-335-5p Inhibits Cell Proliferation, Migration and Invasion in Colorectal Cancer through Downregulating LDHB.

Zhang D ，Yang N 《-》

Circular RNA circ_0007142 regulates cell proliferation, apoptosis, migration and invasion via miR-455-5p/SGK1 axis in colorectal cancer.

Colorectal cancer (CRC) is a frequently diagnosed cancer worldwide. Accumulating researches suggested that circular RNA 0007142 (circ_0007142) contributed to the progression and initiation of CRC. However, the molecular mechanism of circ_0007142 in CRC needs further research. Levels of circ_0007142, microRNA-455-5p (miR-455-5p), and serum- and glucocorticoid-induced protein kinase 1 (SGK1) were identified by quantitative real-time PCR. Cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazol-3-ium bromide assay. Flow cytometry assay was used to detect cell apoptosis in SW480 and HCT116 cells. The relative proteins expression was detected by western blot. Cell migration and invasion were evaluated using transwell assay. Moreover, dual-luciferase reporter and RNA immunoprecipitation assays were conducted to determine the relationship between miR-455-5p and circ_0007142 or SGK1. Finally, xenograft tumor model was established to confirm the effect of circ_0007142 on CRC progression in vivo. Circ_0007142 and SGK1 levels were clearly increased, while miR-455-5p level was reduced in CRC tissues and cell lines. Circ_0007142 silencing promoted cell apoptosis and inhibited cell proliferation, migration and invasion, while these effects of circ_0007142 were partially abolished by miR-455-5p inhibitor in CRC cells. Circ_0007142 could sponge miR-455-5p to regulate SGK1 expression. Moreover, the effects of miR-455-5p on cell proliferation, apoptosis, migration and invasion could be partially reversed by SGK1 overexpression. Besides, circ_0007142 knockdown also suppressed the progression of CRC in vivo. Collectively, Circ_0007142/miR-455-5p/SGK1 axis regulated cell proliferation, apoptosis, migration and invasion of CRC cells, providing a probable therapy target for CRC.

Wen T ，Wu H ，Zhang L ，Li K ，Xiao X ，Zhang L ，Zhang Y ... -  《-》