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miRNA-195-5p通过靶向该基因逆转非小细胞肺癌对顺铂的化疗耐药性。

Reversal of Chemotherapy Resistance to Cisplatin in NSCLC by miRNA-195-5p via Targeting the Gene.

作者信息

Wang Hao, Sui Zhi-Lin, Wu Xian-Xian, Tang Peng, Zhang Hong-Dian, Yu Zhen-Tao

机构信息

Department of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy of Tianjin City, Tianjin, 300060, People's Republic of China.

Department of Surgical Oncology, Baotou Cancer Hospital, Baotou, People's Republic of China.

出版信息

Pharmgenomics Pers Med. 2021 Apr 28;14:497-508. doi: 10.2147/PGPM.S302755. eCollection 2021.

Abstract

OBJECTIVE

To explore the mechanism of miR-195-5p in the pathogenesis non-small cell lung cancer (NSCLC) and cisplatin resistance.

METHODS

The function of miR-195-5p in NSCLC and cisplatin resistance were determined by MTT, scratch assay, transwell assay, and nude mice xenograft experiments. miR-195-5p target gene was identified by dual-luciferase reporter assays and real-time PCR analysis.

RESULTS

miR-195-5p content was lower in A549/DDP than that in A549 cells, with reduced chemotherapy sensitivity and increased cell invasion and migration ability. The loss-of-function and gain-of-function assays illustrated that miR-195-5p might have increased the chemosensitivity to cisplatin in the A549/DDP cells and decreased cell migration and invasion. FGF2 is a negatively correlated action target of miR-195-5p. miR-195-5p might affect EMT by inhibiting FGF2. Overexpression of FGF2 resulted in enhanced cisplatin resistance in the cells, while miR-195-5p might have reversed this resistance.

CONCLUSION

Overall, miR-195-5p might target FGF2 to reduce cisplatin resistance in A549/DDP cells and enhance chemosensitivity.

摘要

目的

探讨miR-195-5p在非小细胞肺癌(NSCLC)发病机制及顺铂耐药中的作用机制。

方法

采用MTT法、划痕实验、Transwell实验及裸鼠异种移植实验检测miR-195-5p在NSCLC及顺铂耐药中的作用。通过双荧光素酶报告基因检测和实时定量PCR分析鉴定miR-195-5p的靶基因。

结果

A549/DDP细胞中miR-195-5p含量低于A549细胞,化疗敏感性降低,细胞侵袭和迁移能力增强。功能缺失和功能获得实验表明,miR-195-5p可能增加A549/DDP细胞对顺铂的化疗敏感性,并降低细胞迁移和侵袭能力。FGF2是miR-195-5p的负相关作用靶点。miR-195-5p可能通过抑制FGF2影响上皮-间质转化(EMT)。FGF2过表达导致细胞顺铂耐药性增强,而miR-195-5p可能逆转这种耐药性。

结论

总体而言,miR-195-5p可能靶向FGF2降低A549/DDP细胞的顺铂耐药性并增强化疗敏感性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b49/8092352/a39ee6a0bfe4/PGPM-14-497-g0001.jpg

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