Abstract
We investigated the influence of the long noncoding RNA VPS9D1 antisense RNA 1 (VPS9D1-AS1) on the malignant phenotype of non-small cell lung cancer (NSCLC) cells in vitro and in vivo. We also explored the mechanisms by which VPS9D1-AS1 exerts its oncogenic action during NSCLC progression. VPS9D1-AS1 expression was upregulated in NSCLC; the extent of its upregulation significantly correlated with patients’ adverse clinicopathological characteristics and shorter overall survival. When VPS9D1-AS1 was knocked down in NSCLC cells, their proliferation, colony-forming capacity, migration, and invasiveness were lower, whereas their apoptosis rate was higher, compared to the control. VPS9D1-AS1 knockdown attenuated tumor growth of NSCLC cells in vivo. Mechanistically, VPS9D1-AS1 directly interacted with microRNA-532-3p (miR-532-3p) in NSCLC cells; the impact of VPS9D1-AS1 knockdown on NSCLC cells was attenuated by miR-532-3p inhibition. Furthermore, VPS9D1-AS1 knockdown decreased the expression of high mobility group AT-hook 2 (HMGA2) in NSCLC cells via miR-532-3p sponging. Recovery of HMGA2 expression partially reversed the inhibitory effects of VPS9D1-AS1 knockdown on NSCLC cells. Thus, VPS9D1-AS1 functions as a competing endogenous RNA that positively regulates HMGA2 expression by sponging miR-532-3p in NSCLC cells, suggesting that the VPS9D1-AS1–miR-532-3p–HMGA2 pathway can be a potential diagnostic and/or therapeutic target in NSCLC.
Highlights
Lung cancer is the third most prevalent type of human malignant tumor and a leading cause of cancer-related death among both men and women globally (~18%) [1]
VPS9D1-AS1 directly interacted with microRNA-532-3p in non-small cell lung cancer (NSCLC) cells; the impact of VPS9D1-AS1 knockdown on NSCLC cells was attenuated by miR532-3p inhibition
We focused on the changes in the expression of miR-532-3p as our analysis predicted that this miRNA (Figure 3B) has a high probability of binding to VPS9D1-AS1; in addition, miR532-3p has been reported to play a crucial role in NSCLC progression [28]
Summary
Lung cancer is the third most prevalent type of human malignant tumor and a leading cause of cancer-related death among both men and women globally (~18%) [1]. It was estimated that lung cancer was responsible for approximately 2.1 million new cancer cases and 1.8 million deaths worldwide in 2018 [2]. NSCLC, which accounts for approximately 85% of all lung cancer cases, includes three subtypes, namely adenocarcinoma, squamous cell carcinoma, and large cell carcinoma [4]. Over the past several decades, there have been tremendous advances in targeted therapeutic techniques and the development of new anticancer compounds; NSCLC is still one of the most frequent and deadly malignant tumors with a 5-year overall survival rate below 18% [5]. A more comprehensive understanding of NSCLC pathogenesis is of paramount importance for the identification of novel promising therapeutic targets in this disease
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
