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 quantitati...

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Main Authors: Huaishi Wang, Xi Chen, Baishuang Yang, Zhi Xia, Qiong Chen
Format: Article
Language:English
Published: BMC 2020-10-01
Series:Cancer Cell International
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12935-020-01516-0
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author Huaishi Wang
Xi Chen
Baishuang Yang
Zhi Xia
Qiong Chen
author_facet Huaishi Wang
Xi Chen
Baishuang Yang
Zhi Xia
Qiong Chen
author_sort Huaishi Wang
collection DOAJ
description 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.
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spelling doaj.art-30d5300894cc466494a06e3bc91633e02022-12-21T19:26:36ZengBMCCancer Cell International1475-28672020-10-0120111310.1186/s12935-020-01516-0MiR-924 as a tumor suppressor inhibits non-small cell lung cancer by inhibiting RHBDD1/Wnt/β-catenin signaling pathwayHuaishi Wang0Xi Chen1Baishuang Yang2Zhi Xia3Qiong Chen4Department of Geriatrics, Xiangya Hospital of Central South UniversityRespiratory Medicine, Xiangya Hospital of Central South UniversityDepartment of Geriatrics, Xiangya Hospital of Central South UniversityDepartment of Geriatrics, Xiangya Hospital of Central South UniversityDepartment of Geriatrics, Xiangya Hospital of Central South UniversityAbstract 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.http://link.springer.com/article/10.1186/s12935-020-01516-0miR-924RHBDD1Non-small cell lung cancerWnt/β-catenin signaling
spellingShingle Huaishi Wang
Xi Chen
Baishuang Yang
Zhi Xia
Qiong Chen
MiR-924 as a tumor suppressor inhibits non-small cell lung cancer by inhibiting RHBDD1/Wnt/β-catenin signaling pathway
Cancer Cell International
miR-924
RHBDD1
Non-small cell lung cancer
Wnt/β-catenin signaling
title MiR-924 as a tumor suppressor inhibits non-small cell lung cancer by inhibiting RHBDD1/Wnt/β-catenin signaling pathway
title_full MiR-924 as a tumor suppressor inhibits non-small cell lung cancer by inhibiting RHBDD1/Wnt/β-catenin signaling pathway
title_fullStr MiR-924 as a tumor suppressor inhibits non-small cell lung cancer by inhibiting RHBDD1/Wnt/β-catenin signaling pathway
title_full_unstemmed MiR-924 as a tumor suppressor inhibits non-small cell lung cancer by inhibiting RHBDD1/Wnt/β-catenin signaling pathway
title_short MiR-924 as a tumor suppressor inhibits non-small cell lung cancer by inhibiting RHBDD1/Wnt/β-catenin signaling pathway
title_sort mir 924 as a tumor suppressor inhibits non small cell lung cancer by inhibiting rhbdd1 wnt β catenin signaling pathway
topic miR-924
RHBDD1
Non-small cell lung cancer
Wnt/β-catenin signaling
url http://link.springer.com/article/10.1186/s12935-020-01516-0
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