The predictive function of miR-122-5p and its action mechanism by regulating PKM2 in metabolic syndrome

  • BMC Endocr Disord. 2025 Feb 27;25(1):54. doi: 10.1186/s12902-025-01888-2.
Xinglu Zhou  #  1 ,  Rui Wu  #  2 ,  Guangfeng Tang  3 ,  Tongtong Shen  4 ,  Wei Li  5
Affiliations
  • 1. Department of Endocrinology, Shanghai Pudong New Area Gongli Hospital, Shanghai, 200135, China.
  • 2. Nursing Department, Geriatric Hospital Affiliated with Wuhan University of Science and Technology, Wuhan, 430065, China.
  • 3. Endocrinology Department, The Affiliated Chuzhou Hospital of Anhui Medical University, Chuzhou, 239000, China.
  • 4. Cardiovascular Medicine, The Affiliated Chuzhou Hospital of Anhui Medical University, No. 369, West Drunken Weng Road, Nanqiao District, Chuzhou, Anhui, 239001, China. [email protected].
  • 5. Department of Endocrinology, Huanggang Central Hospital Affiliated to Yangtze University, No.6, Qi'an Avenue, Huangzhou District, Huanggang, Hubei Province, 438000, China. [email protected].
  • # Contributed equally.
PMID: 40011864 DOI: 10.1186/s12902-025-01888-2
Abstract

Background: Obesity will cause metabolic syndrome (Mets) easily, and its pathogenesis is not completely clear.

Aim: To probe into the predictive value of miR-122-5p and its regulatory mechanism in Mets.

Method: The predictive effect of miR-122-5p on Mets was evaluated by constructing a Receiver Operating Characteristic (ROC) curve. The target genes of miR-122-5p were predicted using the ENCORI/starBase and TargetScanHuman databases, and Pyruvate Kinase M2 (PKM2), closely related to Mets, was screened by GO and KEGG analysis. The roles of miR-122-5p/PKM2 in Insulin resistance (IR) were explored by treating the human normal liver cells (HLCs) with palmitic acid (PA) to induce the IR model. The effects of miR-122-5p/PKM2 on glucose metabolism (GM) of HLCs were evaluated by detecting the production of pyruvic acid, lactic acid, and ATP.

Results: MiR-122-5p was highly expressed in obese people and Mets patients, and its predicted AUC for Mets was 0.876. In HLCs transfected with wild-type PKM2 luciferase vector (PKM2-wt), luciferase activity was attenuated by the miR-122-5p mimic and enhanced by its inhibitor. The expression of PKM2 was inhibited by the miR-122-5p mimic and up-regulated by its inhibitor. The miR-122-5p mimic enhanced PA-induced IR and inhibited the GM of HLCs, which were reversed by overexpression of PKM2. The miR-122-5p inhibitor exerted the opposite effects of its mimic, which were also reversed by silencing of PKM2.

Conclusion: MiR-122-5p, a risk factor for Mets, mediated the IR and abnormal glucose metabolism of HLCs by negatively regulating PKM2.

Clinical trial number: Not applicable.

Keywords
Glucose metabolism; Insulin resistance; Metabolic syndrome; Obesity; PKM2; miR-122-5p.
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