Long non‐coding RNA NEAT1 promotes aerobic glycolysis and progression of cervical cancer through WNT/β‐catenin/PDK1 axis

• Published in: Cancer medicine (Malden, MA) MA), 2024-05, Vol.13 (9), p.e7221-n/a
• Main Authors: Su, Min, Liang, Ziyan, Shan, Shidong, Gao, Yang, He, Li, Liu, Xuelian, Wang, Anjin, Wang, Hua, Cai, Hongbing
• Format: Article
• Language: English
• Subjects: Antibodies; beta Catenin - genetics; beta Catenin - metabolism; Cell cycle; Cell Line, Tumor; Cell migration; Cell Movement; Cell Proliferation; Cervical cancer; Cholecystokinin; Disease Progression; Female; Flow cytometry; Gene Expression Regulation, Neoplastic; Glucose; Glycolysis; Humans; Immunofluorescence; Immunohistochemistry; Membranes; Metastases; Metastasis; Molecular modelling; NEAT1; Non-coding RNA; PDK1; Plasmids; Proteins; Pyruvate Dehydrogenase Acetyl-Transferring Kinase - genetics; Pyruvate Dehydrogenase Acetyl-Transferring Kinase - metabolism; Pyruvic acid; Reagents; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Signal transduction; Tricarboxylic acid cycle; Tumor cell lines; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - metabolism; Uterine Cervical Neoplasms - pathology; Western blotting; Wnt protein; Wnt Signaling Pathway; WNT/β‐catenin; β-Catenin
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.7221

Background Cervical cancer is one of the most common gynecological cancers. Accumulated evidence shows that long non‐coding RNAs (lncRNAs) play essential roles in cervical cancer occurrence and progression, but their specific functions and mechanisms remain to be further explored. Methods The RT‐qPCR assay was used to detect the expression of NEAT1 in cervical cancer tissues and cell lines. CCK‐8, colony formation, flow cytometry, western blotting, and Transwell assays were used to evaluate the impact of NEAT1 on the malignant behavior of cervical cancer cells. Glucose consumption, lactate production, ATP levels, ROS levels, MMP levels, and the mRNA expressions of glycolysis‐related genes and tricarboxylic acid cycle‐related genes were detected to analyze the effect of NEAT1 on metabolism reprograming in cervical cancer cells. The expressions of PDK1, β‐catenin and downstream molecules of the WNT/β‐catenin signaling pathway in cervical cancer cells and tissues were detected by western blotting, RT‐qPCR, immunofluorescence and immunohistochemistry assays. Results This study investigated the role and possible molecular mechanism of lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in cervical cancer. Our results showed that NEAT1 was highly expressed in cervical cancer tissues and cell lines. Downregulation of NEAT1 inhibited the proliferation, migration, invasion and glycolysis of cervical cancer cells, while overexpression of NEAT1 led to the opposite effects. Mechanistically, NEAT1 upregulated pyruvate dehydrogenase kinase (PDK1) through the WNT/β‐catenin signaling pathway, which enhanced glycolysis and then facilitated cervical cancer metastasis. Furthermore, NEAT1 maintained the protein stability of β‐catenin but did not affect its mRNA level. We also excluded the direct binding of NEAT1 to the β‐catenin protein via RNA pull‐down assay. The suppressive impact of NEAT1 knockdown on cell proliferation, invasion, and migration was rescued by β‐catenin overexpression. The WNT inhibitor iCRT3 attenuated the carcinogenic effect induced by NEAT1 overexpression. Conclusion In summary, these findings indicated that NEAT1 may contribute to the progression of cervical cancer by activating the WNT/β‐catenin/PDK1 signaling axis. In this article, we focused on the essential role and specific mechanism of NEAT1 in metabolism reprograming. We highlighted the vital role of WNT/β‐catenin pathway in the regulation of aerobic glycolysis through targeting the key enz