LncRNA CYP4A22-AS1 promotes the progression of lung adenocarcinoma through the miR-205-5p/EREG and miR-34c-5p/BCL-2 axes

Liyao Dong; Lin Zhang; Xinyun Zhao; Hongling Zou; Sisi Lin; Xinping Zhu; Jili Cao; Chun Zhou; Zhihong Yu; Yongqiang Zhu; Kequn Chai; Mingqian Li; Qun Li

doi:10.1186/s12935-023-03036-z

LncRNA CYP4A22-AS1 promotes the progression of lung adenocarcinoma through the miR-205-5p/EREG and miR-34c-5p/BCL-2 axes

Cancer Cell Int. 2023 Sep 5;23(1):194. doi: 10.1186/s12935-023-03036-z.

Authors

Liyao Dong^{1

2}, Lin Zhang³, Xinyun Zhao^{1

2}, Hongling Zou^{1

2}, Sisi Lin², Xinping Zhu², Jili Cao², Chun Zhou⁴, Zhihong Yu², Yongqiang Zhu², Kequn Chai², Mingqian Li⁵, Qun Li⁶

Affiliations

¹ College of Life Science, Sichuan Normal University, Chengdu, 610101, Sichuan, China.
² Zhejiang Provincial Key Laboratory of Cancer Prevention and Treatment Technology of Integrated Traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, 310012, Zhejiang, China.
³ Hebei Province Key Laboratory of Research and Development for Chinese Medicine, Institute of Traditional Chinese Medicine, Chengde Medical College, Chengde, 067000, Hebei, China.
⁴ People's Liberation Army Joint Logistic Support Force 903th Hospital, Hangzhou, 330000, Zhejiang, China.
⁵ Zhejiang Provincial Key Laboratory of Cancer Prevention and Treatment Technology of Integrated Traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, 310012, Zhejiang, China. limingqian613@163.com.
⁶ College of Life Science, Sichuan Normal University, Chengdu, 610101, Sichuan, China. liqun01234@163.com.

Abstract

Objectives: Lung adenocarcinoma (LUAD) exhibits a higher fatality rate among all cancer types worldwide, yet the precise mechanisms underlying its initiation and progression remain unknown. Mounting evidence suggests that long non-coding RNAs (lncRNAs) exert significant regulatory roles in cancer development and progression. Nevertheless, the precise involvement of lncRNA CYP4A22-AS1 in LUAD remains incompletely comprehended.

Methods: Bioinformatics analyses evaluated the expression level of CYP4A22-AS1 in lung adenocarcinoma and paracancer. The LUAD cell line with a high expression of CYP4A22-AS1 was constructed to evaluate the role of CYP4A22-AS1 in the proliferation and metastasis of LUAD by CCK8, scratch healing, transwell assays, and animal experiments. We applied transcriptome and microRNA sequencing to examine the mechanism of CYP4A22-AS1 enhancing the proliferation and metastasis of LUAD. Luciferase reporter gene analyses, west-blotting, and qRT-PCR were carried out to reveal the interaction between CYP4A22-AS1, miR-205-5p/EREG, and miR-34c-5p/BCL-2 axes.

Results: CYP4A22-AS1 expression was significantly higher in LUAD tissues than in the adjacent tissues. Furthermore, we constructed a LUAD cell line with a high expression of CYP4A22-AS1 and noted that the high expression of CYP4A22-AS1 significantly enhanced the proliferation and metastasis of LUAD. We applied transcriptome and microRNA sequencing to examine the mechanism of CYP4A22-AS1 enhancing the proliferation and metastasis of LUAD. CYP4A22-AS1 increased the expression of EREG and BCL-2 by reducing the expression of miR-205-5p and miR-34-5p and activating the downstream signaling pathway of EGFR and the anti-apoptotic signaling pathway of BCL-2, thereby triggering the proliferation and metastasis of LUAD. The transfection of miR-205-5p and miR-34-5p mimics inhibited the role of CYP4A22-AS1 in enhancing tumor progression.

Conclusion: This study elucidates the molecular mechanism whereby CYP4A22-AS1 overexpression promotes LUAD progression through the miR-205-5p/EREG and miR-34c-5p/BCL-2 axes.

Keywords: BCL-2; CYP4A22-AS1; EREG; Lung adenocarcinoma; miR-205-5p; miR-34c-5p.

Abstract

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