MicroRNA-148b regulates tumor growth of non-small cell lung cancer through targeting MAPK/JNK pathway

Abstract

Background MicroRNA-148b (miR-148b) has been detected in various types of tumors, and is generally viewed as a tumor suppressor. Our previous study found the decreased expression of miR-148b in human non small cell lung cancer (NSCLC) specimens and cell lines. However, the underlying mechanisms of miR-148b in regulating tumor progression remain unclear. Methods Firstly animal experiments were performed to verify whether miR-148b could inhibit the tumor growth. Then, the underlying mechanisms were studied by transfecting recombinant plasmids containing a miR-148b mimic or a negative control (NC) mimic (shRNA control) into NSCLC cell lines PC14/B and A549 cells. Tumor cells transfected with unpackaged lentiviral vectors was used as blank control. Cell proliferation capabilities were measured by using CCK-8 kit and colony formation assay. Cell cycle arrest was compared to clarify the mechanism underlying the tumor cell proliferation. Annexin V-FITC Apoptosis Detection kit was applied to investigate the effect of miR-148b on cell apoptosis. Furthermore, western blot analysis were performed to study the targeting pathway. Results We found that over-expression of miR148b could significantly inhibit tumor growth, while knocking down miR148b could obviously promote tumor growth. Further experiment showed that miR-148b inhibited tumor cell proliferation. Besides, over-expression of miR148b decreased the G2/M phase population of the cell cycle by preventing NSCLC cells from entering the mitotic phase and enhanced tumor cell apoptosis. Further western blot analysis indicated that miR148b could inhibit mitogen-activated protein kinase/Jun N-terminal kinase (MAPK/JNK) signaling by decreasing the expression of phosphorylated (p) JNK. Conclusions These results demonstrate that miR-148b could inhibit the tumor growth and act as tumor suppressor by inhibiting the proliferation and inducing apoptosis of NSCLC cells by blocking the MAPK/JNK pathway.

Long non-coding RNA AC122108.1 promotes lung adenocarcinoma brain metastasis and progression through the Wnt/β-catenin pathway by directly binding to aldolase A

“…A study showed that β-catenin knockdown inhibited metastatic potential, including migration and invasion, and inhibited the brain metastasis of PC14PE6/LvBr4 cells in vivo (20). Further, our results indicated that AC122108.1 is downregulated in PC14/B cells, a highly brain metastatic cell line of LAD, which significantly suppressed the proliferative, invasive, and metastatic potential of these cells (21,22). The results of in vivo and in vitro experiments demonstrated that AC122108.1 plays an important role in regulating the proliferation, cell cycle, apoptosis, invasiveness, migration, and metastasis of LAD.…”

MicroRNA-148b Inhibits the Malignant Biological Behavior of Melanoma by Reducing Sirtuin 7 Expression Levels

“…This suggests that miR-148b plays an important role in cancer dynamics, including melanoma. In non-small-cell lung cancer, miR-148b suppresses tumor growth and metastasis by regulating the NF- κ B and MAPK/JNK pathways [ 28 , 29 ]. Leong et al reported that miR-148a/b-3p targets an isoform of RAS-like protein (RALBP1) and thus functions as a tumor suppressor in oral squamous cell carcinomas [ 30 ].…”

Involvement of phosphatase and tensin homolog-induced putative kinase 1/Parkin-mediated autophagy in angiotensin II-induced cardiac hypertrophy in C57BL/6 mice

“…The effect of Ang II on myocardial apoptosis in mice was determined by using the Annexin V-FITC/PI cell apoptosis detection kit (KeyGEN BioTECH, Nanjing, China) according to a protocol used previously. 10…”