Abstract:
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.
journal_name
Thorac Cancerjournal_title
Thoracic cancerauthors
Wang XH,Gan CZ,Xie JYdoi
10.1111/1759-7714.12824subject
Has Abstractpub_date
2018-12-01 00:00:00pages
1583-1593issue
12eissn
1759-7706issn
1759-7714journal_volume
9pub_type
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