微小RNA hsa-miR-93靶向STAT3提高鼻咽癌对放疗敏感性的机制研究

doi:10.11904/j.issn.1002-3070.2023.01.004

Abstract

Abstract: Objective The Objective of this study was to study the role and molecular mechanism of hsa-miR-93 in radiotherapy resistance of nasopharyngeal carcinoma(NPC). Methods Human NPC cell lines CNE-1,CNE-2,CNE-2R,HONE1,C666.1 and nasopharyngeal epithelial immortalized NP460 cell line were used as the research objects.The expression of hsa-miR-93 after radiotherapy in each group of cells was detected by qRT-PCR;The expression of STAT3 protein after radiotherapy in each group of cells was detected by Western blot;MiRwalk software and RNAHybrid software were used to predict the function and binding site of the combination of hsa-miR-93 and STAT3;The binding sites of hsa-miR-93 to STAT3 was detected by dual luciferase reporter gene assay;The expression of STAT3 was detected by qRT-PCR and Western blot;After the expression of STAT3 was silenced by transfection with siSTAT3,the clonogenic ability of NPC cells after radiotherapy was detected by cell colony formation assay. Results Compared with CNE-1 cells and CNE-2 cells(relative radiotherapy sensitivity),the expression of hsa-miR-93 in HONE1 cells and CNE-2R cells(relative radiotherapy resistance)decreased(P＜0.001),and the expression of hsa-miR-93 in each group was decreased in a dose- and time- dependent manner after radiotherapy(P＜0.05).Compared with CNE-1 cells and CNE-2 cells,the expression of STAT3 increased in HONE1 cells and CNE-2R cells,and the expression of STAT3 in NPC cells of each group after radiotherapy increased in a dose- and time-dependent manner.It was predicted that hsa-miR-93 could directly target STAT3.Overexpression of hsa-miR-93 could significantly inhibit the expression of STAT3 at mRNA and protein levels(P＜0.05),while inhibition of hsa-miR-93 could significantly upregulate the expression of STAT3(P＜0.05).Overexpression of hsa-miR-93 or silencing of STAT3 significantly reduced the number of NPC cell colony(P＜0.001).Inhibition of hsa-miR-93 attenuated the sensitivity of NPC to radiotherapy,while simultaneous inhibition of hsa-miR-93 and STAT3 could increase the sensitivity of NPC to radiotherapy. Conclusion hsa-miR-93 increases the sensitivity of NPC to radiotherapy by targeting STAT3.

Key words: Nasopharyngeal carcinoma, Radiotherapy, microRNA, hsa-miR-93, STAT3

CLC Number:

R739.6

ZHOU Qichun, WANG Xi, DENG Zhiyin, XU Mengfei, TANG Qing, WU Wanyin, WANG Sumei. Research on the mechanism of hsa-miR-93 targeting STAT3 to improve the radiosensitivity of nasopharyngeal carcinoma[J]. Journal of Practical Oncology, 2023, 37(1): 17-25.

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URL: http://journal09.magtechjournal.com/Jwk3_syzlxzz/EN/10.11904/j.issn.1002-3070.2023.01.004

http://journal09.magtechjournal.com/Jwk3_syzlxzz/EN/Y2023/V37/I1/17

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Research on the mechanism of hsa-miR-93 targeting STAT3 to improve the radiosensitivity of nasopharyngeal carcinoma

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