miR-339-5p downregulation contributes to Taxol resistance in small-cell lung cancer by targeting α1,2-fucosyltransferase 1.

Lung cancer is a leading cause of cancer-related mortality, and non-small-cell lung carcinoma is responsible for almost 80% of lung cancer-related deaths. In recent years, lung cancer has shown increasing incidence but poor prognosis, and many studies have demonstrated that microRNAs play crucial roles in the development of lung carcinoma and chemoresistance. This study investigated the role of miR-339-5p involvement in lung carcinoma cell lines and chemoresistance to Taxol. We observed that miR-339-5p was significantly downregulated in Taxol-A549 cells compared with A549 cells. In vitro studies further indicated that miR-339-5p could promote colony formation and attenuate apoptosis of lung carcinoma cell lines through targeting α1,2-fucosyltransferase 1 and regulation of the downstream protein Lewis y. Furthermore, miR-339-5p was found to enhance the proliferation inhibition ability of Taxol in lung carcinoma cell lines as well as in the Taxol-A549 subclone. An in vivo study indicated that both miR-339-5p and Taxol could attenuate the growth of lung carcinoma; moreover, miR-339-5p could synergistically promote this inhibitory function of Taxol. In summary, our results suggest a miR-339-5p molecular network that is involved in controlling lung carcinoma progression. © 2017 The Authors IUBMB Life published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology, 69(11):841-849, 2017.

Inhibition of miR-24 suppresses malignancy of human non-small cell lung cancer cells by targeting WWOX in vitro and in vivo.

BACKGROUND: We investigated the effect of micro-RNA 24 (miR-24) and WWOX on non-small cell lung cancer (NSCLC) cell proliferation and migration in vitro and in vivo. METHODS: We performed bioinformatics analysis and 3' untranslated region luciferase assay to investigate the direct target of miR-24. Proliferation, apoptosis, and transwell invasion assays were employed to evaluate the effect of WWOX overexpression with pcDNA3-WWOX and knocking down miR-24 with miR-24 small interfering RNA. Quantitative real-time PCR, Western blot, and immunohistochemistry were also used to investigate miR-24 and c-Kit expression, and apoptosis and invasion-related proteins. Finally, we constructed a tumor xenograft model in nude mice to confirm the effect of miR-24 on NSCLC cell proliferation in vivo. RESULTS: According to our experimental data, miR-24 inhibition could induce apoptosis by activating caspase 3 and suppress the viability and proliferation of NSCLC cells in vitro and in vivo. MiR-24 downregulation could reduce the invasive ability of NSCLC cells by downregulating MMP9. WWOX was identified as a functional target of miR-24. WWOX overexpression generated the same effect with antagonizing miR-24, while blocking WWOX counteracted the tumor suppressive effect caused by miR-24 inhibition. MiR-24 may function as an oncogene and play an important role in the cell growth and migration of NSCLC. CONCLUSIONS: Our findings enhance understanding of the miR-24 regulatory network and the molecular mechanism that underlies the oncogenesis and development of NSCLC. Suppressing the effect of miR-24 on cancer cells using a miR-24 inhibitor may be an attractive therapeutic strategy against NSCLC.