Downregulation of lncRNA ANRIL represses tumorigenicity and enhances cisplatin‐induced cytotoxicity via regulating microRNA let‐7a in nasopharyngeal carcinoma

Abstract

Many studies have demonstrated that upregulation of long non-coding RNA (lncRNA) antisense non-coding RNA in the INK4 locus (ANRIL) plays an oncogenic role in various tumors, including nasopharyngeal carcinoma (NPC). The aim of this study is to explore the effect of ANRIL in NPC progression and cisplatin (DDP)-induced cytotoxicity. The results showed that ANRIL was highly expressed and let-7a was downregulated in NPC tissues and cells. Luciferase assay revealed that ANRIL could negatively regulate miR-let-7a expression. ANRIL knockdown inhibited NPC cell proliferation and induced apoptosis, while anti-let-7a reversed these effects. Combination treatment of si-ANRIL and DDP led to a lower viability, a more DNA strand breaks damage and a higher comet tail length compared with any single treatment, whereas let-7a inhibitor abolished these effects. Furthermore, depletion of ANRIL exacerbated DDP-induced cytotoxicity in NPC cells in vivo. Taken together, these data indicated that knockdown of ANRIL represses tumorigenicity and enhances DDP-induced cytotoxicity via regulating microRNA let-7a in NPC cells, providing a promising therapeutic strategy for NPC patients.

The Network of Non-coding RNAs in Cancer Drug Resistance

“…Controversely, lncRNAs might also modify drug responsiveness exerting a miRNAs sponge activity acting as ceRNAs. Wang et al demonstrated that downregulation of ANRIL lncRNA enhanced cisplatin citotoxicity via let-7a in nasopharyngeal carcinoma (307). These findings further confirm the role of let-7 family as inhibitors of chemoresistance.…”

Functions and Roles of Long-Non-Coding RNAs in Human Nasopharyngeal Carcinoma

“…This may partially account for ANRIL-induced stem-like NPC cells and tumorigenesis [73]. In addition, knockdown of ANRIL repressed tumorigenicity and enhanced DDP-induced cytotoxicity through regulating microRNA let-7a in NPC cells, this provided a promising therapeutic strategy for NPC patients [54]. Moreover, silencing of ANRIL repressed proliferation, promoted apoptosis, and improved radiosensitivity in NPC cells via functioning as a miR-125a sponge [74].…”

“…Furthermore, HOTAIR also promoted angiogenesis through directly activating the transcription of angiogenic factor VEGFA as well as GRP78-mediated induction of VEGFA and Ang2 expressions in NPC cells [68]. Studies have demonstrated that upregulation of lncRNA antisense non-coding RNA in the INK4 locus (ANRIL) played an oncogenic role in various tumors, including NPC [54, 70-72]. LncRNA ANRIL, which encodes a 3834-nt RNA that contains 19 exons at the antisense orientation of the INK4B-ARF-INK4A gene cluster, could promote NPC progression by increasing cell proliferation and transformation, reprogramming cell glucose metabolism, and inducing side-population stem-like cancer cells.…”

“…Nevertheless, the mechanism of MEG3 as a tumor suppressor warrants further studies. LncRNA-LET, a recently identified 1ncRNA, has also been shown to act as a tumor suppressor in NPC as well [54, 55]. LET inhibited proliferation, adhesion and invasion of NPC in vitro by enhancing its expression.…”

circRNAs Signature as Potential Diagnostic and Prognostic Biomarker for Diabetes Mellitus and Related Cardiovascular Complications

“…In addition, as with any treatment, it is anticipated that circRNAs as drugs might also cause unwanted side effects and modify drug responsiveness or cause resistance. For instance, downregulation of ANRIL lncRNA was shown to enhance cisplatin cytotoxicity via let-7a in nasopharyngeal carcinoma [107]. In the coming years, our understanding of circRNA dynamic networks may grow and new biological roles may emerge.…”