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微小 RNA-181b 通过靶向血管紧张素转换酶 2 对小细胞肺癌生物学特性及临床耐药性的影响。

Effect of microRNA-181b on the biological characteristics and clinical drug resistance of small-cell lung cancer by targeting angiotensin converting enzyme 2.

机构信息

The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.

Department of Thoracic Surgery, Hebei General Hospital, Shijiazhuang, Hebei, China.

出版信息

Thorac Cancer. 2022 Mar;13(5):742-749. doi: 10.1111/1759-7714.14313. Epub 2022 Jan 17.

Abstract

OBJECTIVE

To clarify the effect of miR-181b on the biological function of small-cell lung cancer (SCLC) and explore the effect of clinical resistance on SCLC.

METHODS

Blood samples were collected from 30 SCLC patients and 30 non-SCLC patients in our department from 2017 to 2019 to detect the expression level of miR-181b.The expression level of miR-181b was detected in SCLC cells by RT-PCR, and screening of downstream target genes by gene chip, verification with luciferase, and Western blotting. In addition, collect the general data of 30 SCLC patients and 30 non-SCLC patients (control group), the patients were diagnosed by pathology and undergoing EC protocol in the Department of Thoracic Surgery and Oncology of our hospital to detect the expression level of mir-181b in different periods. Furthermore, in the SCLC cell line, EC chemotherapy was administered to detect the sensitivity of drug resistance and nondrug resistance.

RESULTS

miR-181b in SCLC patients was lower than in normal people as well as the drug-sensitive cell line. ACE2 was verified as a downstream target of miR-181b by gene chip screening. First-line chemotherapy can promote the recovery of miR-181b, but cannot repair to normal levels. miR-181b can enhance the drug sensitivity of SCLC drug-resistant cells.

CONCLUSION

miR-181b directly targets ACE2 to affect the biological characteristics of SCLC. The expression level of miR-181b is highly related to the drug resistance of SCLC, which suggests that miR-181b could be a potential biomarker candidate for treatment efficacy of SCLC.

摘要

目的

阐明 miR-181b 对小细胞肺癌(SCLC)生物学功能的影响,并探讨其对 SCLC 临床耐药性的影响。

方法

收集 2017 年至 2019 年我科收治的 30 例 SCLC 患者和 30 例非 SCLC 患者的血样,检测 miR-181b 的表达水平。采用 RT-PCR 检测 SCLC 细胞中 miR-181b 的表达水平,通过基因芯片筛选下游靶基因,通过荧光素酶和 Western blot 进行验证。此外,收集 30 例 SCLC 患者和 30 例非 SCLC 患者(对照组)的一般资料,患者经病理诊断,在我院胸外科及肿瘤科行 EC 方案化疗,检测不同时期 mir-181b 的表达水平。进一步在 SCLC 细胞系中进行 EC 化疗,检测耐药和非耐药细胞的药物敏感性。

结果

SCLC 患者 miR-181b 低于正常人及药敏细胞系。通过基因芯片筛选验证 ACE2 是 miR-181b 的下游靶基因。一线化疗可以促进 miR-181b 的恢复,但不能恢复到正常水平。miR-181b 可增强 SCLC 耐药细胞的药物敏感性。

结论

miR-181b 通过直接靶向 ACE2 影响 SCLC 的生物学特性。miR-181b 的表达水平与 SCLC 的耐药性高度相关,提示 miR-181b 可能是 SCLC 治疗效果的潜在生物标志物候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cd2/8888155/efc2ed5ae28f/TCA-13-742-g003.jpg

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