Dowregulation of OTX1 attenuates gastric cancer cell proliferation, migration and invasion.

Orthodenticle homolog 1 (OTX1) has previously been revealed to be tightly associated with the development and progression of several human tumors. However, the functional roles and underlying molecular mechanisms of OTX1 in gastric cancer (GC) remain poorly understood. In the present study, we observed that OTX1 was highly expressed in GC tissues compared with adjacent non­tumor tissues based on a large cohort of samples from The Cancer Genome Atlas (TCGA) database. An immunohistochemical analysis indicated that OTX1 levels were increased in tumors that became metastatic compared with those in tumors that did not. This finding was significantly associated with patients who had shorter overall survival times. The knockdown of OTX1 significantly inhibited the proliferation, migration and invasion of SGC­7901 and MGC­803 cells. Furthermore, the knockdown of OTX1 induced cell cycle arrest in the G0/G1 phase and reduced the expression of cyclin D1. In addition, the inhibition of OTX1 led to increased GC cell apoptosis by upregulating cleaved PARP, cleaved caspase­3 and Bax. In conclusion, our data indicated that OTX1 functions as a key regulator in tumor growth and metastasis of GC cells. Thus, OTX1 may be a promising novel target for molecular therapy directed toward GC.

Decrease expression of microRNA-20a promotes cancer cell proliferation and predicts poor survival of hepatocellular carcinoma.

BACKGROUND: Growing evidences indicate microRNAs play important roles in cancer development, progression, metastasis and may constitute robust biomarkers for cancer prognosis. The aim of this study was to identify the clinical and functional association of microRNA-20a (miR-20a) in hepatocellular carcinoma (HCC). METHODS: MiR-20a was detected using Taqman real-time polymerase chain reaction. Kaplan-Meier and Cox proportional regression analyses were utilized to determine the association of miR-20a with survival of patients. The potential functions of miR-20a on proliferation were evaluated by proliferation and flow cytometry analysis. The direct target gene of miR-20a was also identified by luciferase reporter assays. RESULTS: MiR-20a was lower in primary HCC than normal liver, and were further decreased in those with post-liver transplantation (LT) HCC recurrence compared with those with non-recurrence (p = 0.001). Patients with lower miR-20a expression had significantly poorer recurrence-free survival (RFS, Log rank p < 0.001) and overall survival (OS, Log rank p < 0.001). Multivariate analysis revealed that lower miR-20a was an independent predictor of poor prognosis. MiR-20a restoration could suppress HepG2 and SMMC-7721 cells proliferation and induce cell cycle G1 arrest and apoptosis. Subsequent investigations revealed that miR-20a directly targeted myeloid cell leukemia sequence 1 (Mcl-1) and reduced the endogenous protein level of Mcl-1 in HCC cells. CONCLUSIONS: MiR-20a is decreased in HCCs and correlates with HCC recurrence and prognosis. Down-regulation of miR-20a increases the proliferation abilities of HCC cells. Our findings suggest miR-20a may represent a novel potential therapeutic target and biomarker for survival of HCC patients.