Wang Huaishi, Chen Xi, Yang Baishuang, Xia Zhi, Chen Qiong
Department of Geriatrics, Xiangya Hospital of Central South University, NO 87 Xiangya Road, Changsha, China.
Respiratory Medicine, Xiangya Hospital of Central South University, Changsha, China.
Cancer Cell Int. 2020 Oct 8;20:491. doi: 10.1186/s12935-020-01516-0. eCollection 2020.
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.
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.
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.
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.
据报道，miR-924在肝细胞癌中是一种肿瘤抑制因子。然而，miR-924在非小细胞肺癌（NSCLC）中的功能和机制仍不清楚。
采用定量实时PCR检测NSCLC组织和细胞系中miR-924的表达。采用卡方检验评估NSCLC患者miR-924水平与临床病理参数之间的相关性。通过CCK-8法评估细胞增殖。通过Transwell法检测细胞迁移和侵袭。通过荧光素酶报告基因检测分析miR-924与RHBDD1的结合。利用Oncomine的公共微阵列数据集评估肺癌组织中RHBDD1的表达水平，并通过Kaplan-Meier Plotter数据库评估其预后价值。建立肿瘤异种移植小鼠模型以阐明miR-924对NSCLC体内肿瘤发生的影响。
在本研究中，我们发现miR-924在NSCLC组织和细胞系中显著降低。miR-924降低与NSCLC患者的晚期肿瘤-淋巴结-转移（TNM）分期和淋巴转移密切相关。值得注意的是，含菱形结构域蛋白1（RHBDD1）被预测并确认为miR-924的直接靶点。此外，利用Oncomine和Kaplan-Meier Plotter数据库的公共微阵列数据集，RHBDD1的表达水平显著升高且与预后呈负相关。miR-924过表达抑制细胞增殖、迁移和侵袭。体内实验进一步证明，miR-924过表达通过抑制RHBDD1/Wnt/β-连环蛋白信号通路降低NSCLC异种移植瘤的生长。
总之，这些发现表明miR-924通过靶向RHBDD1阻断NSCLC的进展，miR-924/RHBDD1轴可能为NSCLC的治疗提供一个新的治疗靶点。
