Open Access

CCR4‑NOT transcription complex subunit 2 regulates TRAIL sensitivity in non‑small‑cell lung cancer cells via the STAT3 pathway

  • Authors:
    • Eun‑Ok Kim
    • Shi‑Eun Kang
    • Minji Choi
    • Ki‑Jong Rhee
    • Miyong Yun
  • View Affiliations

  • Published online on: December 12, 2019     https://doi.org/10.3892/ijmm.2019.4425
  • Pages: 324-332
  • Copyright: © Kim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

TRAIL is an attractive candidate for anticancer therapy in a variety of tumors since it targets only tumors and not normal tissue. However, a remaining major hurdle is that the majority of tumors exhibit a resistance mechanism against the effects of TRAIL via the induction of anti‑apoptotic signaling pathways. In this study, we aimed to evaluate whether the modulation of CCR4‑NOT transcription complex subunit 2 (CNOT2) function can promote TRAIL sensitivity in non‑small‑cell lung cancer (NSCLC) cells. CNOT2 depletion partially decreased colony numbers and the proliferation of NSCLC cells. When combined with TRAIL, the suppression of CNOT2 expression markedly decreased the survival rate and increased apoptosis, as compared with TRAIL treatment alone in TRAIL‑resistant NSCLC cells. Of note, CNOT2 overexpression in TRAIL‑sensitive H460 cells enhanced the survival rate and decreased apoptosis when compared with TRAIL treatment alone. Gene expression analysis indicated that genes involved in the signal transducer and activator of transcription 3 (STAT3) signaling pathway were dominantly altered in the CNOT2‑depleted A549 cells. Under this condition, Src homology region 2 domain containing phosphatase‑1 (SHP1) was significantly upregulated and subsequently increased apoptosis. On the whole, the findings of this study demonstrate that CNOT2 participates in TRAIL sensitivity in NSCLC cells via the regulation of the STAT3 signaling pathway, and suggest that combination therapy with CNOT2 depletion and TRAIL treatment may prove to be a useful strategy for overcoming TRAIL resistance in NSCLC.
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February 2020
Volume 45 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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APA
Kim, E., Kang, S., Choi, M., Rhee, K., & Yun, M. (2020). CCR4‑NOT transcription complex subunit 2 regulates TRAIL sensitivity in non‑small‑cell lung cancer cells via the STAT3 pathway. International Journal of Molecular Medicine, 45, 324-332. https://doi.org/10.3892/ijmm.2019.4425
MLA
Kim, E., Kang, S., Choi, M., Rhee, K., Yun, M."CCR4‑NOT transcription complex subunit 2 regulates TRAIL sensitivity in non‑small‑cell lung cancer cells via the STAT3 pathway". International Journal of Molecular Medicine 45.2 (2020): 324-332.
Chicago
Kim, E., Kang, S., Choi, M., Rhee, K., Yun, M."CCR4‑NOT transcription complex subunit 2 regulates TRAIL sensitivity in non‑small‑cell lung cancer cells via the STAT3 pathway". International Journal of Molecular Medicine 45, no. 2 (2020): 324-332. https://doi.org/10.3892/ijmm.2019.4425