Open Access

CRNDE silencing promotes apoptosis and enhances cisplatin sensitivity of colorectal carcinoma cells by inhibiting the Akt/mTORC1‑mediated Warburg effect

  • Authors:
    • Wenyu Yang
    • Yanchun Wang
    • Chunhui Tao
    • Yunhai Li
    • Shan Cao
    • Xiqian Yang
  • View Affiliations

  • Published online on: January 5, 2022     https://doi.org/10.3892/ol.2022.13190
  • Article Number: 70
  • Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Colorectal cancer (CRC) is one of the most prevalent gastrointestinal tumors worldwide, with a high mortality rate. The lncRNA colorectal neoplasia differentially expressed (CRNDE) is upregulated in CRC and is involved in regulating the apoptosis, proliferation, and drug sensitivity of CRC cells. However, the specific underlying mechanisms remain to be elucidated. The aim of the present study was to investigate the effects of CRNDE on the Warburg effect in CRC cells, as well as the associated mechanisms. The expression of CRNDE in HCT‑116 cells was overexpressed or silenced by transfection. Apoptosis, cisplatin sensitivity, the Warburg effect, and Akt/mTOR activation were evaluated. The results demonstrated that CRNDE inhibition decreased the proliferation and increased the apoptosis and cisplatin sensitivity of HCT‑116 cells. In addition, CRNDE inhibition attenuated the Warburg effect in HCT‑116 cells, as verified by a decrease in ATP production, lactic acid levels, glucose uptake, and the expression of Warburg effect‑related enzymes (GLUT1, LDHA, HK2, and PKM2). CRNDE inhibition also suppressed the activity of the Akt/mTORC1 pathway, as demonstrated by the decreased phosphorylation of Akt, S6K, S6, and mTOR and the increased phosphorylation of 4EBP‑1 and EIF‑4E. The CRNDE overexpression‑induced increase in ATP and lactic acid levels and glucose uptake in HCT‑116 cells was reversed by Akt and mTOR inhibitors. These findings indicate that CRNDE silencing promotes apoptosis and enhances cisplatin sensitivity in colorectal carcinoma cells, which may be mediated by the regulation of the Warburg effect via the Akt/mTORC1 pathway. The present study thus provides a potential strategy for the treatment of CRC.
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February-2022
Volume 23 Issue 2

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Yang W, Wang Y, Tao C, Li Y, Cao S and Yang X: CRNDE silencing promotes apoptosis and enhances cisplatin sensitivity of colorectal carcinoma cells by inhibiting the Akt/mTORC1‑mediated Warburg effect. Oncol Lett 23: 70, 2022
APA
Yang, W., Wang, Y., Tao, C., Li, Y., Cao, S., & Yang, X. (2022). CRNDE silencing promotes apoptosis and enhances cisplatin sensitivity of colorectal carcinoma cells by inhibiting the Akt/mTORC1‑mediated Warburg effect. Oncology Letters, 23, 70. https://doi.org/10.3892/ol.2022.13190
MLA
Yang, W., Wang, Y., Tao, C., Li, Y., Cao, S., Yang, X."CRNDE silencing promotes apoptosis and enhances cisplatin sensitivity of colorectal carcinoma cells by inhibiting the Akt/mTORC1‑mediated Warburg effect". Oncology Letters 23.2 (2022): 70.
Chicago
Yang, W., Wang, Y., Tao, C., Li, Y., Cao, S., Yang, X."CRNDE silencing promotes apoptosis and enhances cisplatin sensitivity of colorectal carcinoma cells by inhibiting the Akt/mTORC1‑mediated Warburg effect". Oncology Letters 23, no. 2 (2022): 70. https://doi.org/10.3892/ol.2022.13190