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Upregulation of MCL-1 by LUCAT1 through interacting with SRSF1 promotes the migration and invasion in non-small cell lung carcinoma

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Abstract

The onset of non-small cell lung carcinoma (NSCLC) still be in the fog. LUCAT1 is potentially capable of modulating MCL-1-involved NSCLC pathogenesis via targeting SRSF1. Also, MCL-1 can regulate Wnt/β-catenin pathway to affect the tumorigenesis of NSCLC. Thus, this paper aims to uncover an intriguing and novel role of LUCAT1/SRSF1/MCL-1 axis in NSCLC based on Wnt/β-catenin pathway. A549 and NCI-H1650, two cell lines of NSCLC, were used to mimic NSCLC in vitro. MCL-1 siRNA (si-MCL-1) and LUCAT1 siRNA (si-LUCAT1) were used to downregulate MCL-1 and LUCAT1 in NSCLC cells, respectively. The overexpression vector of SRSF1 based on pcDNA 3.1 was constructed to upregulate SRSF1 expression. 40 μM SKL2001 was used to activate Wnt/β-catenin pathway. Transwell assay was used for migrative and invasive tests. The effect of LUCAT1 on tumor metastasis was verified in nude mice. MCL-1 downregulation led to the decrease of EMT, invasion, and migration in NSCLC, while Wnt/β-catenin pathway agonist partially reversed the effects of MCL-1 downregulation. Mechanistic investigations revealed that LUCAT1 and MCL-1 mRNA were enriched in SRSF1; LUCAT1 silence decreased MCL-1, whereas SRSF1 enhancement elevated MCL-1; Importantly, SRSF1 overexpression significantly reversed MCL-1 alteration due to LUCAT1 silence. In NSCLC cells, SRSF1 overexpression offset the si-LUCAT1-induced changes, and si-MCL-1 reversed the SRSF1-induced cellular changes. Further, LUCAT1 inhibition reduced lung metastasis of cancer cells. LUCAT1 can interact with SRSF1 to regulate MCL-1 expression that targets the Wnt/β-catenin pathway-mediated NSCLC cell migration, invasion, and EMT.

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Data Availability

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

Code Availability

Not applicable.

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Acknowledgements

We would like to thank the anonymous reviewers who have helped to improve the paper.

Funding

This work was supported by Guangxi Qihuang Scholar Cultivation Project, the Youth Science Funding Project of National Natural Science Foundation of China (82004296), the Key Subject Construction Project of Guangxi Traditional Chinese Medicine (GZXK-P-20-07), the Doctoral Scientific Research Foundation of Guangxi University of Chinese Medicine (2020BS029), the Youth Foundation of Self-funded Scientific Research Subject of Guangxi Health Commission (Z20200260), the Doctoral Scientific Research Foundation of The First Affiliated Hospital of Guangxi University of Chinese Medicine (2020BS006), and the Self-funded Scientific Research Subject of Guangxi Administration of Traditional Chinese Medicine (GXZYA20220073).

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Author notes

  1. Fang Fang and Mei Zhao are co-first authors.

Authors and Affiliations

  1. The Second Ward of Oncology, The First Affiliated Hospital of Guangxi University of Chinese Medicine, No. 327, Xianhu Avenue, Qingxiu District, Nanning, 530001, Guangxi Zhuang Autonomous Region, People’s Republic of China

    Fang Fang, Zhixin Dong, Jiaxiao Wang & Wei Shi

  2. Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, 530001, Guangxi Zhuang Autonomous Region, People’s Republic of China

    Mei Zhao

  3. Department of Traditional Chinese Medicine, Yunnan Cancer Hospital, Kunming, 650018, Yunnan Province, People’s Republic of China

    Xiaowei Jin

  4. Guangxi University of Chinese Medicine, Nanning, 530001, Guangxi Zhuang Autonomous Region, People’s Republic of China

    Jinming Meng

  5. Preventive Treatment of Disease Center, The First Affiliated Hospital of Guangxi University of Chinese Medicine, No. 89-9, Dongge Road, Qingxiu District, Nanning, 530023, Guangxi Zhuang Autonomous Region, People’s Republic of China

    Sheng Xie

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Contributions

Guarantor of integrity of the entire study: Sheng Xie. Study concepts: Wei Shi, Jiaxiao Wang. Study design: Fang Fang. Definition of intellectual content: Fang Fang. Literature research: Xiaowei Jin. Experimental studies: Fang Fang, Xiaowei Jin, Zhixin Dong, Jinming Meng. Data acquisition: Mei Zhao, Jinming Meng. Data analysis: Mei Zhao. Statistical analysis: Mei Zhao. Manuscript preparation: Fang Fang. Manuscript editing: Fang Fang. Manuscript review: Fang Fang

Corresponding authors

Correspondence to Sheng Xie or Wei Shi.

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The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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The animal experimental protocol was approved by the Ethics Committee of The First Affiliated Hospital of Guangxi University of Chinese Medicine.

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Fang, F., Zhao, M., Jin, X. et al. Upregulation of MCL-1 by LUCAT1 through interacting with SRSF1 promotes the migration and invasion in non-small cell lung carcinoma. Mol Cell Biochem (2023). https://doi.org/10.1007/s11010-023-04851-8

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