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

Eun Ok Kim, Shi Eun Kang, Minji Choi, Ki Jong Rhee, Miyong Yun

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)324-332
Number of pages9
JournalInternational journal of molecular medicine
Volume45
Issue number2
DOIs
Publication statusPublished - 2020

Bibliographical note

Publisher Copyright:
© 2020 Spandidos Publications. All rights reserved.

All Science Journal Classification (ASJC) codes

  • Genetics

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