LncRNA RHPN1-AS1 promotes the progression of nasopharyngeal carcinoma by targeting CELF2 expression

Exp Mol Pathol. 2021 Oct:122:104671. doi: 10.1016/j.yexmp.2021.104671. Epub 2021 Aug 4.

Abstract

This study aims to investigate the role of lncRNA RHPN1-AS1 in NPC and its potential regulatory mechanism. The expression of RHPN1-AS1 in tissues and cells was measured by qRT-PCR. The effect of RHPN1-AS1 silencing on biological functions of NPC cells was detected by CCK-8, colony formation, flow cytometry, wound healing, and transwell assays. The protein expression was measured by western blot. The RBPs of RHPN1-AS1 were predicted by Starbase and LncTar, and verify by RIP assay. ESTIMATE was used to analyze the relationship between CELF2 expression and tumor purity. GSEA was used to analyze the downstream signaling pathway of CELF2. In our study, RHPN1-AS1 was up-regulated in NPC tissues and cells. RHPN1-AS1 silencing inhibited cell viability, capacity of proliferation, migration and invasion, promoted apoptosis, decreased protein expression of Bcl-2, MMP2/9, increased protein expression of Bax, caspase-3, and TIMP2 of NPC cells. CELF2 was a target of RHPN1-AS1 and was down-regulated in NPC tissues and cells. CELF2 level was associated with tumor purity negatively. Low expression of CELF2 activated mTORC1 signaling pathway and increased protein expression of p-mTORC1/mTORC1 and p-P70S6K/P70S6K. RHPN1-AS1 silencing eliminated the activating effect of CELF2 silencing on mTORC1 signaling pathway. Moreover, CELF2 silencing reversed the inhibitory effect of RHPN1-AS1 on NPC progression. In conclusion, our findings indicated that RHPN1-AS1 plays an important role in NPC via activating mTORC1 signaling which is modulated by CELF2. RHPN1-AS1 may serve as a potential therapeutic target for NPC treatment.

Keywords: CELF2; Nasopharyngeal carcinoma; RHPN1-AS1; mTORC1.

MeSH terms

  • Adult
  • Aged
  • CELF Proteins / genetics*
  • Carcinogenesis / genetics*
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Male
  • Mechanistic Target of Rapamycin Complex 1 / genetics
  • Middle Aged
  • Nasopharyngeal Carcinoma / genetics*
  • Nasopharyngeal Carcinoma / pathology
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Nerve Tissue Proteins / genetics*
  • RNA, Long Noncoding / genetics*
  • RNA-Binding Proteins / genetics

Substances

  • CELF Proteins
  • CELF2 protein, human
  • Nerve Tissue Proteins
  • RNA, Long Noncoding
  • RNA-Binding Proteins
  • Mechanistic Target of Rapamycin Complex 1