While it is known that miR-203 is frequently downregulated in many types of human cancer, little is known regarding its expression and functional role in colorectal cancer (CRC). In this study, we aimed to investigate the expression and the potential mechanisms of miR-203 in colorectal cancer. MiR-203 was significantly downregulated in CRC tissues compared with matched normal adjacent tissues. Our clinical data show that decreased miR-203 was associated with an advanced clinical tumor-node-metastasis stage, lymph node metastasis, and poor survival in CRC patients. Furthermore, externally induced expression of miR-203 significantly inhibited CRC cell proliferation and invasion in vitro and in vivo. Mechanistically, we identified EIF5A2 as a direct and functional target of miR-203. The levels of miR-203 were inversely correlated with levels of the EIF5A2 in the CRC tissues. Restoration of EIF5A2 in the miR-203-overexpressing CRC cells reversed the suppressive effects of miR-203. Our results demonstrate that miR-203 serves as a tumor suppressor gene and may be useful as a new potential therapeutic target in CRC.

Previous studies have shown that the expression of miR-211 was downregulated in hepatocellular carcinoma (HCC). However, the molecular function and mechanism of miR-211 in HCC growth and invasion are largely unclear. We found that miR-211 is downregulated in HCC tissues and cell lines, respectively. Further results showed that low miR-211 associated with TNM stage, vein invasion status, and poor prognosis. Ectopic expression of miR-211 effectively suppressed HCC cell proliferation, migration and invasion both in vitro and in vivo. We identified SPARC as a bona fide target of miR-211, and overexpression of miR-211 decreased the mRNA and protein expression of SPARC. Finally, we confirmed that the overexpression of SPARC in miR-211-expressing HCC cells can partially restore the inhibitory effect of miR-211. Taken together, our results demonstrated that loss of miR-211 expression and thus uncontrolled SPARC overexpression might drive progression of HCC, which may provide a novel therapeutic strategy for the treatment of HCC.

Dysregulation of microRNAs has been reported to be involved in the progression of human colorectal cancers (CRCs). Loss of the adenomatous polyposis coli (APC) gene is a common initiating event in CRCs. PTEN inactivation by mutation or allelic loss also occurs in CRCs. miR‑135b was reported to be upregulated in CRCs and its overexpression was due to APC/β‑catenin and PTEN/PI3K pathway deregulation. APC was proven to be a target of miR‑135b and forms a feedback loop with miR‑135b. In the present study, we found that ubiquitin‑specific peptidase 13 (USP13) was a target of miR‑135b. miR‑135b downregulated the expression of USP13, and reduced the stability of PTEN. miR‑135b promoted cell proliferation and glycolysis that could be reversed by the overexpression of USP13 or PTEN. Moreover, knockdown of USP13 upregulated the levels of endogenous miR‑135b, but not those in CRC cells with PTEN mutation. The results showed positive feedback loops between miR‑135b and PTEN inactivation in CRCs.

No abstract

Triple functional domain protein (TRIO) is an evolutionarily conserved Dbl family guanine nucleotide exchange factors (GEFs) involved in cell proliferation and progression of some types of cancer. However, the expression and prognostic role of TRIO in hepatocellular carcinoma (HCC) have not yet been determined. Therefore, we attempted to determine the impact of TRIO on the clinical outcome of HCC patients to further identify its role in HCC. TRIO expression was examined using quantitative real-time PCR (qRT-PCR) and Western blotting in nonmalignant liver cells, HCC cells, and 93 paired of HCC tissues and adjacent noncancerous tissues. Statistical analyses were used to assess associations between TRIO expression and clinicopathological and prognostic factors. Small interfering RNA (siRNA)-mediated TRIO inhibition was performed in Hep3B and Huh7 cells to elucidate its roles in HCC. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was employed to measure cell proliferation, and apoptosis assay was analyzed by flow cytometry, respectively. Adhesion and transwell invasion assay were performed to determine the invasion ability of HCC cells in vitro. TRIO was significantly upregulated in the HCC cell lines and tissues compared with the nonmalignant liver cells and adjacent noncancerous liver tissues. In addition, high TRIO expression level associated with lymph node metastasis (P = 0.0183), clinical tumor node metastasis (TNM) stage (P = 0.0.0106), and decrease in overall survival (OS) (P = 0.017). Knockdown of TRIO on Hep3B and Huh7 cell lines suppressed cell proliferation and migration and induced apoptosis. Furthermore, silencing TRIO expression led to decrease of ras-related C3 botulinum toxin substrate 1 (Rac1), p-P38, B cell lymphoma 2 (BCL-2), and matrix metallopeptidase 9 (MMP-9). Our results demonstrated that TRIO protein expression is elevated and associated with a worse over survival rates in patients with HCC. Aberrant expression of TRIO might play an important role in HCC through promoting cell proliferation and invasion, and TRIO may be a novel therapeutic target for the treatment of HCC.