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

• Published in: Journal of cellular physiology Vol. 234; no. 4; pp. 4302 - 4313
• Main Authors: Zhang, Wei‐Yi, Liu, Yin‐Jiao, He, Yan, Chen, Ping
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.04.2019
• Subjects: 3' Untranslated Regions; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Binding Sites; Cancer; Cell proliferation; Cell Proliferation - drug effects; Cervical cancer; Cervix; Chemotherapy; Cisplatin; Cisplatin - pharmacology; cisplatin resistance; DNA microarrays; Drug resistance; Drug Resistance, Neoplasm; Female; Gene Expression Regulation, Neoplastic; HeLa Cells; Homology; Human papillomavirus; Humans; Immunoprecipitation; long noncoding NCK1‐AS1; MicroRNAs - genetics; MicroRNAs - metabolism; microRNA‐134‐5p; MSH2; MSH2 protein; MutS Homolog 2 Protein - genetics; MutS Homolog 2 Protein - metabolism; MutS protein; Nucleotides; Patients; Proteins; Reporter gene; Ribonucleic acid; RNA; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Signal Transduction; siRNA; Transcription; Uterine Cervical Neoplasms - drug therapy; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - metabolism; Uterine Cervical Neoplasms - pathology; MSH2; long noncoding NCK1-AS1; cervical cancer; cisplatin resistance; microRNA-134-5p
• ISSN: 0021-9541; 1097-4652; 1097-4652
• DOI: 10.1002/jcp.27198

Cervical cancer remains a serious health problem till now, with nearly 500,000 women cases diagnosed each year around the world. Long noncoding RNA (lncRNA) is a novel class of RNA transcripts (>200 nucleotides in length) participating in gene transcription, cell proliferation, differentiation, and drug resistance. This study aimed to explore the regulatory relationship among lncRNA NCK1‐AS1, miR‐134‐5p, and MutS protein homolog 2 (MSH2), so that the resistance against cisplatin in cervical cancer treatment could be better understood. Comprehensive lncRNA profiling analysis was performed to screen lncRNAs differentially expressed in cervical cancer. The expression patterns of miR‐134‐5p, NCK1‐AS1, and MSH2 were evaluated in cancerous tissues and adjacent normal tissues obtained from 75 cervical cancer patients. Subsequently, anti‐NCK1‐AS1 small interfering RNA, miR‐134‐5p mimics, and miR‐134‐5p inhibitors were transfected into cervical cancer cells, and the effects of these transcripts on cisplatin resistance and cell apoptosis were investigated. The regulatory relationship among NCK1‐AS1, miR‐134‐5p, and MSH2 was identified using a dual‐luciferase reporter gene assay, and the results were further validated by RNA pull‐down and RNA immunoprecipitation assays. Based on the microarray data of GSE63514 and GSE27678, NCK1‐AS1 was upregulated in cervical cancer. Increased expression of NCK1‐AS1, MSH2, and decreased expression of miR‐134‐5p were observed in cervical cancer tissues. In addition, NCK1‐AS1 competitively bound to miR‐134‐5p to regulate MSH2. Therefore, si‐NCK1‐AS1 and miR‐134‐5p mimic both reduced MSH2 activity and increased cisplatin‐induced apoptosis in cervical cancer cells. Taken together, NCK1‐AS1 may become a novel target in improving the chemotherapeutic response and survival of cervical cancer patients. This study aimed to explore the regulatory relationship among long noncoding RNA NCK1‐AS1, miR‐134‐5p, and MutS protein homolog 2, so that the resistance against cisplatin in cervical cancer treatment could be better understood. NCK1‐AS1 may become a novel target in improving the chemotherapeutic response and survival of cervical cancer patients.