miRNA 146a promotes chemotherapy resistance in lung cancer cells by targeting DNA damage inducible transcript 3 (CHOP).
The underlying molecular mechanism of lung cancer drug resistance is poorly understood. The mediator of endoplasmic reticulum stress CHOP (DNA damage inducible transcript 3) promotes stress-induced apoptosis and appears to function as a transcription factor in multiple diseases. However, its potenti...
| Published in: | Cancer Letters Vol. 428; pp. 55 - 69 |
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| Main Authors: | , , , , , , , , |
| Format: | research Journal Article |
| Published: |
Elsevier B.V.
Aug2018
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=129734700&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 129734700 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 03043835 3J8 jtl: Cancer Letters issn: 03043835 maglogo: N pubinfo: dt: Aug2018 vid: 428 pid: 1004 pub: Elsevier B.V. artinfo: ui: 129734700 129734700 NLM29702190 129734700 10.1016/j.canlet.2018.04.028 NLM29702190 129734700 ppf: 55 ppct: 14 formats: tig: atl: miRNA 146a promotes chemotherapy resistance in lung cancer cells by targeting DNA damage inducible transcript 3 (CHOP). aug: au: Tan, Wenfeng Liao, Yi Qiu, Yang Liu, Hongxiang Tan, Deli Wu, Tao Tang, Meng Zhang, Shixin Wang, Haidong affil: Cardiothoracic Surgery Department, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China sug: subj: RNA Metabolism Proteins Lung Neoplasms Drug Therapy Drug Resistance, Neoplasm Lung Neoplasms Mortality Lung Neoplasms Pathology Biochemical Phenomena Male Genes Drug Effects Genetic Techniques Mice Lung Neoplasms Animal Studies Proteins Metabolism Cell Line, Tumor Lung Pathology Kaplan-Meier Estimator Epithelial Cells Middle Age Female Human Prognosis Validation Studies Comparative Studies Evaluation Research Multicenter Studies Middle Aged: 45-64 years Male Female ab: The underlying molecular mechanism of lung cancer drug resistance is poorly understood. The mediator of endoplasmic reticulum stress CHOP (DNA damage inducible transcript 3) promotes stress-induced apoptosis and appears to function as a transcription factor in multiple diseases. However, its potential contributions to multidrug resistance in solid tumors is unknown. Here, we investigated CHOP expression in tumor tissues form 69 lung cancer patients, finding that deficient CHOP expression is associated with poor prognosis. Cisplatin-resistant lung cancer cells exhibited lower expression of CHOP compared to that in sensitive lung cancer cells, and silencing or augmenting CHOP expression enhanced or impaired cisplatin resistance, respectively. Mechanistic investigations revealed that CHOP is directly associated with the regulation of autophagy or apoptosis-regulatory genes including LC3-II, death receptor 5 (DR5), and telomere repeat-binding factor 3. Notably, CHOP was identified as a target of miR-146a, and increased miR-146a expression in lung cancer cells was suggested to be responsible for CHOP mRNA down-regulation. Further, animal models confirmed that abnormally expressed miR-146a in lung cancer cells does not affect growth, but rather alters chemotherapy sensitivity. Together, CHOP is a useful prognostic marker and miR-146a is a potential therapeutic target for multidrug-resistant lung cancer. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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