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Circ_001042抑制转化生长因子-β1/ p38丝裂原活化蛋白激酶信号轴介导的肺腺癌上皮-间质转化和转移。

Circ_001042 Inhibits TGF-1/P38 MAPK Signaling Axis-Mediated Epithelial-Mesenchymal Transition and Metastasis in Lung Adenocarcinoma.

作者信息

Zhou Lixia, Chen Wenxian, Yang Hang, Liu Jiaqin, Meng Hui

机构信息

Department of Oncology, The Fifth Affiliated (Zhuhai) Hospital of Zunyi Medical University, Zhuhai, Guangdong 519100, China.

Department of Thoracic Surgery, The Fifth Affiliated (Zhuhai) Hospital of Zunyi Medical University. Zhuhai, Guangdong 519100, China.

出版信息

Evid Based Complement Alternat Med. 2022 Aug 4;2022:7890490. doi: 10.1155/2022/7890490. eCollection 2022.

Abstract

OBJECTIVE

To explore the role and molecular mechanism of circ_001042 in lung adenocarcinoma (LUAD).

METHODS

The expression level of circ_001042 and linear RNA MRPS35 in cells and clinical tissues was detected by real-time PCR (qRT-PCR). The expression of circ_001042 and transforming growth factor 1 (TGF-1) in LUAD cells was elevated by the respective transfection of overexpression vectors OE-circ_001042 and TGF-1; MTT and transwell assays were applied to test the proliferation, migration, and invasion abilities of cells, respectively. The E-cadherin expression level in the cells was assessed by immunofluorescence staining, and western blot was utilized to determine the expression level of epithelial-mesenchymal transition (EMT) and TGF-1/P38 MAPK signaling axis-related proteins in the cells.

RESULTS

Circ_001042 was significantly downregulated in LUAD tissues and cells, and high circ_001042 expression could inhibit the proliferation, invasion, and migration of LUAD cells. In addition, circ_001042 also inhibited the EMT process (the E-cadherin level was upregulated; and the levels of N-cadherin, vimentin, and Snail were downregulated) and TGF-1/P38 MAPK signaling axis activity in LUAD cells. Moreover, circ_001042 could suppress the promotion of TGF-1 on the proliferation, invasion, migration, and EMT process of LUAD cells and the activation of TGF-1/P38 MAPK signaling axis.

CONCLUSION

By inhibiting TGF-1, circ_001042 not only suppresses the proliferation, migration, invasion, and EMT of LUAD but also inhibits the activation of TGF-1/P38 MAPK signaling axis. Therefore, circ_001042 can act as a potential target for early diagnosis and targeted therapy of LUAD.

摘要

目的

探讨circ_001042在肺腺癌(LUAD)中的作用及分子机制。

方法

采用实时荧光定量PCR(qRT-PCR)检测细胞和临床组织中circ_001042及线性RNA MRPS35的表达水平。分别转染过表达载体OE-circ_001042和TGF-1来提高LUAD细胞中circ_001042和转化生长因子1(TGF-1)的表达;应用MTT和Transwell实验分别检测细胞的增殖、迁移和侵袭能力。通过免疫荧光染色评估细胞中E-钙黏蛋白的表达水平,利用蛋白质免疫印迹法测定细胞中上皮-间质转化(EMT)及TGF-1/P38丝裂原活化蛋白激酶信号轴相关蛋白的表达水平。

结果

Circ_001042在LUAD组织和细胞中显著下调,高circ_001042表达可抑制LUAD细胞的增殖、侵袭和迁移。此外,circ_001042还抑制LUAD细胞中的EMT过程(E-钙黏蛋白水平上调;N-钙黏蛋白、波形蛋白和Snail水平下调)以及TGF-1/P38 MAPK信号轴活性。此外,circ_001042可抑制TGF-1对LUAD细胞增殖、侵袭、迁移和EMT过程的促进作用以及TGF-1/P38 MAPK信号轴的激活。

结论

通过抑制TGF-1,circ_001042不仅抑制LUAD的增殖、迁移、侵袭和EMT,还抑制TGF-1/P38 MAPK信号轴的激活。因此,circ_001042可作为LUAD早期诊断和靶向治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8675/9371840/16339a3c34be/ECAM2022-7890490.001.jpg

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