Open Access

SOX2 regulates paclitaxel resistance of A549 non‑small cell lung cancer cells via promoting transcription of ClC‑3

  • Authors:
    • Youwei Huang
    • Xiangyu Wang
    • Rendong Hu
    • Guopeng Pan
    • Xi Lin
  • View Affiliations

  • Published online on: September 6, 2022     https://doi.org/10.3892/or.2022.8396
  • Article Number: 181
  • Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Paclitaxel (PTX) is widely used in the treatment of non‑small cell lung cancer (NSCLC). However, acquired PTX drug resistance is a major obstacle to its therapeutic efficacy and the underlying mechanisms are still unclear. The present study revealed a novel role of the SRY‑box transcription factor 2 (SOX2)‑chloride voltage‑gated channel‑3 (ClC‑3) axis in PTX resistance of A549 NSCLC cells. The expression levels of SOX2 and ClC‑3 were upregulated in PTX‑resistant A549 NSCLC cells by RT‑qPCR and western blotting. The drug resistance to PTX of A549 NSCLC cells were measured by detecting the cell viability and the expression of drug resistance markers. Knockdown of SOX2 or ClC‑3 effectively decreased PTX resistance of A549 NSCLC cells, whereas SOX2 or ClC‑3 overexpression promoted PTX resistance. Mechanistically, SOX2 bound to the promoter of ClC‑3 and enhanced the transcriptional activation of ClC‑3 expression by CUT&Tag assays, CUT&Tag qPCR and luciferase reporter. In summary, the present findings defined ClC‑3 as an important downstream effector of SOX2 and ClC‑3 and SOX2 contributed to PTX resistance. Targeting SOX2 and its downstream effector ClC‑3 increased the sensitivity of NSCLC cells to PTX treatment, which provided potential therapeutic strategies for patients with NSCLC with PTX resistance.
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October-2022
Volume 48 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Copy and paste a formatted citation
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Spandidos Publications style
Huang Y, Wang X, Hu R, Pan G and Lin X: SOX2 regulates paclitaxel resistance of A549 non‑small cell lung cancer cells via promoting transcription of ClC‑3. Oncol Rep 48: 181, 2022.
APA
Huang, Y., Wang, X., Hu, R., Pan, G., & Lin, X. (2022). SOX2 regulates paclitaxel resistance of A549 non‑small cell lung cancer cells via promoting transcription of ClC‑3. Oncology Reports, 48, 181. https://doi.org/10.3892/or.2022.8396
MLA
Huang, Y., Wang, X., Hu, R., Pan, G., Lin, X."SOX2 regulates paclitaxel resistance of A549 non‑small cell lung cancer cells via promoting transcription of ClC‑3". Oncology Reports 48.4 (2022): 181.
Chicago
Huang, Y., Wang, X., Hu, R., Pan, G., Lin, X."SOX2 regulates paclitaxel resistance of A549 non‑small cell lung cancer cells via promoting transcription of ClC‑3". Oncology Reports 48, no. 4 (2022): 181. https://doi.org/10.3892/or.2022.8396