MicroRNA-143 promotes apoptosis of osteosarcoma cells by caspase-3 activation via targeting Bcl-2.

Osteosarcoma is the most common malignant bone tumor. In recent years, although a lot of research in the mechanism of osteosarcoma development and metastasis had been done, the molecular mechanisms are still elusive. MicroRNAs (miRs), as small noncoding RNA sequences, are dysregulated in various diseases, including cancer, negatively modulating the target genes expression by posttranscriptional repression. MicroRNA-143 (miR-143) has been reported to be reduced in cancers, including pituitary, colorectal, prostate cancer and cervical. We were aimed to detect the effects of miR-143 on osteosarcoma cell invasion and migration as well as to indicate the potential molecular mechanisms by which miR-143 regulated osteosarcoma. After miR-143 transfection, the cancer cells migration and invasion were examined. And Western blot, RT-PCR, flow cytometry and immunochemistry assays were performed to analyze the role of miR-143 in osteosarcoma progression. The results suggested that miR-143 expressed lessly in osteosarcoma cell lines and could suppress cell migration and invasion in U2-OS and MG-63 cells. To our knowledge, it was the first time to target Bcl-2 directly to explore the underlying mechanism by which miR-143 performed its role to induce apoptosis in tumor cells, thus improving osteosarcoma progression. The present study indicated that miR-143 could inhibit Bcl-2 expression, causing Caspas3 activation, thus inducing apoptosis in osteosarcoma cells. MiR-143 may therefore sreve as a potential biomarker for osteosarcoma, and the regulation of its expression might be a novel therapeutic strategy for osteosarcoma treatment.

Li WH ，Wu HJ ，Li YX ，Pan HG ，Meng T ，Wang X ... -  《-》

MicroRNA-744 inhibited cervical cancer growth and progression through apoptosis induction by regulating Bcl-2.

Growing evidence suggests that microRNA plays an essential role in the development and metastasis of many tumor progressions, including cervical cancer. Aberrant miR-744 expression has been indicated in many growth of tumor, the mechanism of miR-744 inhibits both the proliferation and metastatic ability for cervical cancer remains unclear. Accumulating evidences reported that Bcl-2 signal pathway plays an important role in the cellular process, such as apoptosis, cell growth and proliferation. The goal of this study was to identify miR-744 that could inhibit the growth, migration, invasion, proliferation and metastasis of gastric cancer through targeting Bcl-2 expression. Real-time PCR (RT-qPCR) was used to quantify miR-744 expression in vitro and vivo experiments. The biological functions of miR-744 were determined via cell proliferation. Our study indicated that miR-744 targeted on Bcl-2, which leads to the inactivation of apoptosis signaling and the cell proliferation of cervical cancer cells, ameliorating cervical cancer growth and progression. In addition, both up-regulation of miR-744 and down-regulation of Bcl-2 could stimulate Caspase-3 expression, promoting apoptosis of cervical cancer cells. Therefore, our research revealed the mechanistic links between miR-744 and Bcl-2 in the pathogenesis of cervical cancer through modulation of Caspase-3, leading to the inhibition of cervical cancer cell growth. And targeting miR-744 could be served as a novel strategy for future cervical cancer therapy clinically.

Chen XF ，Liu Y 《-》

MicroRNA-34a inhibits tumor invasion and metastasis in osteosarcoma partly by effecting C-IAP2 and Bcl-2.

Wen J ，Zhao YK ，Liu Y ，Zhao JF ... -  《-》

LncRNA TUG1 promotes cell proliferation and suppresses apoptosis in osteosarcoma by regulating miR-212-3p/FOXA1 axis.

LncRNA taurine upregulated gene 1 (TUG1) was reported to act as a possible oncogene in osteosarcoma (OS) development. However, the underlying molecular basis of TUG1 involved in the progression of OS remains to be thoroughly investigated. The expressions of TUG1 and miR-212-3p in OS tissues and cells were examined by RT-qPCR. Cell proliferation, apoptosis, caspase-3 activity, protein levels of BCL2, Bax, and forkhead box A1 (FOXA1) were detected by colony formation assay, MTT assay, flow cytometry analysis, caspase-3 activity assay, and western blot. Luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RT-qPCR were used to explore the interaction between TUG1, FOXA1 and miR-212-3p. Tumor xenograft mouse model was used to confirm the biological role of TUG in OS in vivo. Elevated TUG1 and FOXA1 expression and reduced miR-212-3p expression were observed in OS tissues and cells. TUG1 knockdown suppressed OS cell proliferation and promoted apoptosis. TUG1 functioned as a ceRNA of miR-212-3p and suppressed miR-212-3p expression. miR-212-3p inhibition reversed the effect of TUG1 knockdown on OS cell proliferation and apoptosis. In addition, FOXA1 was identified as a target of miR-212-3p and TUG1 functioned as a ceRNA to upregulate FOXA1 by sponging miR-212-3p in OS cells. FOXA1 up-regulation abolished the effects of miR-212-3p on OS cell proliferation and apoptosis. TUG1 promoted OS cell proliferation and suppressed apoptosis by regulating the miR-212-3p/FOXA1 axis. Therefore, TUG1/miR-212-3p/FOXA1 axis may be a promising therapeutic target in OS treatment.

Xie C ，Chen B ，Wu B ，Guo J ，Cao Y ... -  《-》

Long non-coding RNA PVT1 promotes osteosarcoma development by acting as a molecular sponge to regulate miR-195.

Zhou Q ，Chen F ，Zhao J ，Li B ，Liang Y ，Pan W ，Zhang S ，Wang X ，Zheng D ... -  《Oncotarget》