lncRNA MNX1‑AS1 promotes prostate cancer progression through regulating miR‑2113/MDM2 axis

Mol Med Rep. 2022 Jul;26(1):231. doi: 10.3892/mmr.2022.12747. Epub 2022 May 26.

Abstract

A growing number of dysregulated long non‑coding (lnc)RNAs have been verified to serve an essential role in human prostate cancer. However, the underlying mechanisms of lncRNA MNX1 Antisense RNA 1 (MNX1‑AS1) in prostate cancer has not been explored. Therefore, the present study aimed to explore the function of MNX1‑AS1 in prostate cancer tumorigenesis and investigate the in‑depth mechanism. The expression of MNX1‑AS1, microRNA (miR)‑2113 and murine double min 2 (MDM2) in prostate cancer tissues and corresponding normal tissues were assessed by reverse transcription‑quantitative PCR. The protein expression levels of MDM2 were detected by western blotting. LNCaP and PC‑3 cells were transfected with short hairpin (sh)‑MNX1‑AS1, miR‑2113 mimics, miR‑2113 inhibitor and pCDH‑MDM2 vector using Lipofectamine® 3000. Cell proliferation, migration and invasion abilities were assessed by CCK‑8 assay, colony formation and Transwell assay, respectively. Dual luciferase reporter assay was carried out to confirm the putative targets of MNX1‑AS1 and miR‑2113. Tumor formation experiment in nude mice was applied to evaluate the tumor growth effect of MNX1‑AS1 in vivo. The expression of MNX1‑AS1 was significantly upregulated in the prostate cancer tissues and cell lines. MNX1‑AS1 knockdown suppressed the abilities of cell viability and migration and invasion in vitro and inhibited tumor growth in vivo. Additionally, luciferase reporter assay revealed that MNX1‑AS1 could target miR‑2113 and negatively interacted with miR‑2113 in prostate cancer cells. miR‑2113 directly targeted to MDM2 and negatively modulated the expression of MDM2. Rescue assays suggested that the viability, migration and invasion of impaired cells triggered by transfection with sh‑MNX1‑AS1 alone could be recovered by co‑transfection with sh‑MNX1‑AS1 + miR‑2113 inhibitor or sh‑MNX1‑AS1 + pCDH‑ MDM2 vector. The present study demonstrated that MNX1‑AS1 promoted prostate cancer progression through regulating miR‑2113/ MDM2 axis.

Keywords: lncRNA MNX1 antisense RNA 1; microRNA 2113; murine double min‑2; prostate cancer.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Homeodomain Proteins / genetics
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Prostatic Neoplasms* / pathology
  • Proto-Oncogene Proteins c-mdm2 / genetics
  • Proto-Oncogene Proteins c-mdm2 / metabolism
  • RNA, Antisense / genetics
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Transcription Factors / genetics

Substances

  • Homeodomain Proteins
  • MNX1 protein, human
  • MicroRNAs
  • RNA, Antisense
  • RNA, Long Noncoding
  • Transcription Factors
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2

Grants and funding

Funding: No funding was received.