Open Access

VIM‑AS1 promotes proliferation and drives enzalutamide resistance in prostate cancer via IGF2BP2‑mediated HMGCS1 mRNA stabilization

  • Authors:
    • Sheng-Jia Shi
    • Dong-Hui Han
    • Jing-Liang Zhang
    • Yu Li
    • An-Gang Yang
    • Rui Zhang
  • View Affiliations

  • Published online on: January 30, 2023     https://doi.org/10.3892/ijo.2023.5482
  • Article Number: 34
  • Copyright: © Shi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

VIM‑AS1, a cancer‑specific long non‑coding RNA, has been recognized as a pivotal regulator in multiple types of cancer. However, the role of VIM‑AS1 in the proliferation and resistance to anti‑androgen therapy of LNCaP and C4‑2 prostate cancer cells remains to be determined. In the current study, gain‑and‑loss experiments were used to investigate the effects of VIM‑AS on the proliferation and anti‑androgen therapy of LNCaP and C4‑2 cells. RNA sequencing, RNA pulldown and RNA immunoprecipitation were used to elucidate the underlying mechanism of VIM‑AS1 driving prostate progression. It was demonstrated that VIM‑AS1 was upregulated in C4‑2 cells, an established castration‑resistant prostate cancer (CRPC) cell line, compared with in LNCaP cells, an established hormone‑sensitive prostate cancer cell line. The present study further demonstrated that VIM‑AS1 was positively associated with the clinical stage of prostate cancer. Functionally, overexpression of VIM‑AS1 decreased the sensitivity to enzalutamide treatment and enhanced the proliferation of LNCaP cells in vitro, whereas knockdown of VIM‑AS1 increased the sensitivity to enzalutamide treatment and reduced the proliferation of C4‑2 cells in vitro and in vivo. Mechanistically, 3‑hydroxy‑3‑methylglutaryl‑CoA synthase 1 (HMGCS1) was identified as one of the direct downstream targets of VIM‑AS1, and VIM‑AS1 promoted HMGCS1 expression by enhancing HMGCS1 mRNA stability through a VIM‑AS1/insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2)/HMGCS1 RNA‑protein complex. Rescue assays indicated that knockdown of HMGCS1 expression ameliorated the increase in proliferation and enzalutamide resistance of prostate cancer cells induced by VIM‑AS1 overexpression. Overall, the present study determined the roles and mechanism of the VIM‑AS1/IGF2BP2/HMGCS1 axis in regulating proliferation and enzalutamide sensitivity of prostate cancer cells and suggested that VIM‑AS1 may serve as a novel therapeutic target for the treatment of patients with CRPC.
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March-2023
Volume 62 Issue 3

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Spandidos Publications style
Shi S, Han D, Zhang J, Li Y, Yang A and Zhang R: VIM‑AS1 promotes proliferation and drives enzalutamide resistance in prostate cancer via IGF2BP2‑mediated HMGCS1 mRNA stabilization. Int J Oncol 62: 34, 2023
APA
Shi, S., Han, D., Zhang, J., Li, Y., Yang, A., & Zhang, R. (2023). VIM‑AS1 promotes proliferation and drives enzalutamide resistance in prostate cancer via IGF2BP2‑mediated HMGCS1 mRNA stabilization. International Journal of Oncology, 62, 34. https://doi.org/10.3892/ijo.2023.5482
MLA
Shi, S., Han, D., Zhang, J., Li, Y., Yang, A., Zhang, R."VIM‑AS1 promotes proliferation and drives enzalutamide resistance in prostate cancer via IGF2BP2‑mediated HMGCS1 mRNA stabilization". International Journal of Oncology 62.3 (2023): 34.
Chicago
Shi, S., Han, D., Zhang, J., Li, Y., Yang, A., Zhang, R."VIM‑AS1 promotes proliferation and drives enzalutamide resistance in prostate cancer via IGF2BP2‑mediated HMGCS1 mRNA stabilization". International Journal of Oncology 62, no. 3 (2023): 34. https://doi.org/10.3892/ijo.2023.5482