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KLF4通过抑制MSI2和调节JAK/STAT3信号通路来抑制非小细胞肺癌细胞的增殖和转移。

KLF4 suppresses the proliferation and metastasis of NSCLC cells via inhibition of MSI2 and regulation of the JAK/STAT3 signaling pathway.

作者信息

Luo Di-Di, Zhao Feng

机构信息

Department of Medical Oncology, The Frist People's Hospital of Xiangtan, Xiangtan 411101, Hunan, PR China.

Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1277, Jiefang Avenue, Wuhan 430022, Hubei, PR China.

出版信息

Transl Oncol. 2022 Aug;22:101396. doi: 10.1016/j.tranon.2022.101396. Epub 2022 May 14.

DOI:10.1016/j.tranon.2022.101396
PMID:35580385
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9117691/
Abstract

BACKGROUND

Non-small cell lung cancer (NSCLC) remains an aggresive tumor with poor survival rates. Krüppel-like factor 4 (KLF4) is known to be involved in progression of NSCLC; however, the detailed mechanism by which KLF4 regulates the progression of NSCLC remains unclear.

METHODS

In order to investigate the function of KLF4 in NSCLC, cell proliferation was measured by MTT and colony formation assays. The migration and invasion of NSCLC cells were detected via wound healing and Transwell assays, respectively. Then, the interaction between KLF4 and MSI2 was confirmed using a dual-luciferase reporter assay, and the mechanism by which KLF4 regulates the tumorigenesis of NSCLC was assessed by RT-qPCR and Western blotting.

RESULTS

The results showed that KLF4 was downregulated, while MSI2 was upregulated in NSCLC. Additionally, KLF4 could inhibit transcription of MSI2, and overexpression of KLF4 or knockdown of MSI2 could inhibit the proliferation, migration and invasion of NSCLC cells. Moreover, KLF4 could inhibit JAK2/STAT3 signalling pathway.

CONCLUSIONS

In conclusion, KLF4 significantly inhibited the proliferation, invasion and migration of NSCLC cells via inactivation of MSI2/JAK2/STAT3 signalling pathway. Thereby, our finding might shed new lights on exploring the new strategies against NSCLC.

摘要

背景

非小细胞肺癌（NSCLC）仍然是一种侵袭性肿瘤，生存率较低。已知Krüppel样因子4（KLF4）参与NSCLC的进展；然而，KLF4调节NSCLC进展的详细机制仍不清楚。

方法

为了研究KLF4在NSCLC中的功能，通过MTT和集落形成试验检测细胞增殖。分别通过伤口愈合试验和Transwell试验检测NSCLC细胞的迁移和侵袭。然后，使用双荧光素酶报告基因试验证实KLF4与MSI2之间的相互作用，并通过RT-qPCR和蛋白质免疫印迹法评估KLF4调节NSCLC肿瘤发生的机制。

结果

结果显示，在NSCLC中KLF4表达下调，而MSI2表达上调。此外，KLF4可抑制MSI2的转录，过表达KLF4或敲低MSI2可抑制NSCLC细胞的增殖、迁移和侵袭。而且，KLF4可抑制JAK2/STAT3信号通路。

结论

总之，KLF4通过使MSI2/JAK2/STAT3信号通路失活，显著抑制NSCLC细胞的增殖、侵袭和迁移。因此，我们的发现可能为探索抗NSCLC的新策略提供新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b02/9117691/3773b60d3291/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b02/9117691/19941f5de46f/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b02/9117691/1b23452a0c14/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b02/9117691/7382ed392583/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b02/9117691/25d9ba12cbf2/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b02/9117691/c4771d1f401f/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b02/9117691/3773b60d3291/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b02/9117691/19941f5de46f/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b02/9117691/1b23452a0c14/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b02/9117691/7382ed392583/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b02/9117691/25d9ba12cbf2/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b02/9117691/c4771d1f401f/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b02/9117691/3773b60d3291/gr6.jpg

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