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Suppression of long noncoding RNA NCK1-AS1 increases chemosensitivity to cisplatin in cervical cancer

Wei-Yi Zhang1, Yin-Jiao Liu1, Yan He1

  • 1Department of Gynecology and Obstetrics, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China.

Journal of Cellular Physiology
|September 18, 2018
PubMed

Insights

Long noncoding RNA NCK1-AS1 promotes cisplatin resistance in cervical cancer by regulating miR-134-5p and MSH2. Targeting NCK1-AS1 may improve treatment outcomes and patient survival.

Area of Science:

  • Molecular Biology
  • Oncology
  • RNA Biology

Background:

  • Cervical cancer is a significant global health issue, with nearly 500,000 new cases annually.
  • Long noncoding RNAs (lncRNAs) are emerging as key regulators in various cellular processes, including gene transcription and drug resistance.
  • Understanding the molecular mechanisms underlying cisplatin resistance in cervical cancer is crucial for improving therapeutic efficacy.

Purpose of the Study:

  • To investigate the regulatory network involving lncRNA NCK1-AS1, miR-134-5p, and MutS protein homolog 2 (MSH2) in cervical cancer.
  • To elucidate the role of this network in conferring resistance to cisplatin chemotherapy.
  • To explore NCK1-AS1 as a potential therapeutic target for enhancing cervical cancer treatment.

Main Methods:

  • lncRNA profiling analysis to identify differentially expressed lncRNAs in cervical cancer.
  • Quantitative evaluation of NCK1-AS1, miR-134-5p, and MSH2 expression in patient tissues and cell lines.
  • Functional assays including transfection with small interfering RNA (siRNA) and mimics/inhibitors, dual-luciferase reporter assays, RNA pull-down, and RNA immunoprecipitation.

Main Results:

  • NCK1-AS1 was found to be upregulated in cervical cancer tissues.
  • Increased expression of NCK1-AS1 and MSH2, with decreased miR-134-5p, was observed in cancerous tissues.
  • NCK1-AS1 directly interacts with miR-134-5p, regulating MSH2 expression. Inhibition of NCK1-AS1 or augmentation of miR-134-5p reduced MSH2 activity and enhanced cisplatin-induced apoptosis.

Conclusions:

  • The NCK1-AS1/miR-134-5p/MSH2 axis plays a critical role in regulating cisplatin resistance in cervical cancer.
  • NCK1-AS1 acts as a molecular sponge for miR-134-5p, leading to increased MSH2 expression and chemoresistance.
  • Targeting NCK1-AS1 presents a promising strategy for overcoming cisplatin resistance and improving patient survival in cervical cancer.
Keywords:
MSH2cervical cancercisplatin resistancelong noncoding NCK1-AS1microRNA-134-5p

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