MiR-924 as a tumor suppressor inhibits non-small cell lung cancer by inhibiting RHBDD1/Wnt/β-catenin signaling pathway

Abstract

Background MiR-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. Methods The 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. Results In 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. Conclusions In 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.

Circ_0000463 contributes to the progression and glutamine metabolism of non‐small‐cell lung cancer by targeting miR‐924/SLC1A5 signaling

“…We confirmed the associated relation between circ_0000463 and miR‐924. Previous studies reported that miR‐924 suppressed the progression of hepatocellular carcinoma 11 and NSCLC 12 . Consistently, we found that miR‐924 overexpression inhibited the biological properties of NSCLC cells.…”

“…Through bioinformatics analysis, miR‐924 was predicted as a potential target of circ_0000463 in this study. Previous articles reported that miR‐924 plays an anti‐tumor role in hepatocellular carcinoma 11 and NSCLC 12 . For example, Fan et al demonstrated that lncRNA n335586 contributes to hepatocellular carcinoma development by absorbing miR‐924, 11 indicating the anti‐tumor role of miR‐924 in hepatocellular carcinoma.…”

“…For example, Fan et al demonstrated that lncRNA n335586 contributes to hepatocellular carcinoma development by absorbing miR‐924, 11 indicating the anti‐tumor role of miR‐924 in hepatocellular carcinoma. miR‐924 is reported to reduce the malignant potential of NSCLC cells by negatively regulating RHBDD1 expression and inactivating Wnt/β‐catenin pathway 12 . Here, we tested the binding relationship between circ_0000463 and miR‐924 in NSCLC cells and further explored their functional correlation in NSCLC progression.…”

“…Previous articles reported that miR‐924 plays an anti‐tumor role in hepatocellular carcinoma 11 and NSCLC. 12 For example, Fan et al demonstrated that lncRNA n335586 contributes to hepatocellular carcinoma development by absorbing miR‐924, 11 indicating the anti‐tumor role of miR‐924 in hepatocellular carcinoma. miR‐924 is reported to reduce the malignant potential of NSCLC cells by negatively regulating RHBDD1 expression and inactivating Wnt/β‐catenin pathway.…”

SMG9 Serves as an Oncogene to Promote the Tumor Progression via EMT and Wnt/β-Catenin Signaling Pathway in Hepatocellular Carcinoma

“…Meanwhile, there is a strong connection between EMT and HCC (Tong et al, 2020). The Wnt/β-catenin signaling pathway is involved in the development of various human cancers and one of the most well-characterized oncogenic pathway in HCC (Hoshida et al, 2009;Huang et al, 2019;Bi et al, 2020;Wang et al, 2020). A variety of key cellular processes including proliferation, apoptosis, migration and invasion are involved in the progression of HCC in a Wnt/β-catenin-dependent manner (Huang et al, 2020;Lin et al, 2020).…”