Abstract
BackgroundMiR-924 has been reported to be a tumor suppressor in hepatocellular carcinoma. However, the functions and mechanisms of miR-924 in non-small cell lung cancer (NSCLC) remain unclear.MethodsThe expression of miR-924 was determined in NSCLC tissues and cell lines using quantitative real time PCR. The Chi-squared test was used to evaluate the correlation between miR-924 levels and clinicopathological parameters in patients with NSCLC. Cell proliferation was assessed by CCK-8 assay. Cell migration and invasion were detected by transwell assay. The combination of miR-924 and RHBDD1 was analyzed via the luciferase reporter assay. The expression level of RHBDD1 was evaluated in lung cancer tissues using public microarray datasets form Oncomine and its prognostic value was assessed by Kaplan–Meier Plotter databases. A tumor xenograft mouse model was established to illustrate the effects of miR-924 on the tumorigenesis of NSCLC in vivo.ResultsIn this study, we found miR-924 was strikingly decreased in NSCLC tissues and cell lines. Decreased miR-924 was closely correlated with advanced tumor-node-metastasis (TNM) stage and lymphatic metastasis in NSCLC patients. Noticeably, rhomboid domain-containing protein 1 (RHBDD1) was predicted and confirmed as a direct target of miR-924. Moreover, the expression level of RHBDD1 was significantly increased and inversely associated with prognosis using public microarray datasets form Oncomine and Kaplan–Meier Plotter databases. MiR-924 overexpression suppressed cell proliferation, migration and invasion. The in vivo experiments further demonstrated that miR-924 overexpression reduced NSCLC xenograft growth through inhibiting RHBDD1/Wnt/β-catenin signaling pathway.ConclusionsIn summary, these findings demonstrated that miR-924 blocked the progression of NSCLC by targeting RHBDD1 and miR-924/RHBDD1 axis might provide a novel therapeutic target for the treatment of NSCLC.
Highlights
MiR-924 has been reported to be a tumor suppressor in hepatocellular carcinoma
In summary, these findings demonstrated that miR-924 blocked the progression of non-small cell lung cancer (NSCLC) by targeting rhomboid domain-containing protein 1 (RHBDD1) and miR-924/RHBDD1 axis might provide a novel therapeutic target for the treatment of NSCLC
MiR‐924 was significantly down‐regulated in NSCLC tissues and cell lines The expression level of miR-924 was measured in 79 pairs of frozen NSCLC tissues and adjacent lung tissues using quantitative real time PCR
Summary
The functions and mechanisms of miR-924 in non-small cell lung cancer (NSCLC) remain unclear. Jiang et al revealed a tumor suppressive role of miR-449b-5p that restricts the growth and invasion of breast cancer cells through inhibiting CREPT-mediated activation of Wnt/βcatenin [9]. LncRNA n335586 promoted hepatocellular carcinoma cell migration and invasion through facilitating the expression of its host gene CKMT1A by competitively binding miR-924 in HBVrelated hepatocellular carcinoma [13]. It is still unclear whether miR-924 plays a role as a tumor suppressor gene or an oncogene in NSCLC
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