The miR-146a-associated HDAC2 regulation of PI3K is involved in pancreatitis in vitro

Ding-Wen Zhong; Xiang-Tian Zeng; Wen-Hui Chen; Xian-Yu Huang; Jia-Xin Liu; Yong-Hui Liao

doi:10.1016/j.bbrep.2025.102057

The miR-146a-associated HDAC2 regulation of PI3K is involved in pancreatitis in vitro

Biochem Biophys Rep. 2025 May 20:42:102057. doi: 10.1016/j.bbrep.2025.102057. eCollection 2025 Jun.

Authors

Ding-Wen Zhong¹, Xiang-Tian Zeng², Wen-Hui Chen¹, Xian-Yu Huang¹, Jia-Xin Liu¹, Yong-Hui Liao¹

Affiliations

¹ Department of Hepatopancreatobiliary Surgery, Ganzhou People's Hospital, Ganzhou, 341000, Jiangxi, China.
² Central Supply Service Department, Ganzhou People's Hospital, Ganzhou, 341000, Jiangxi, China.

Abstract

Purpose: To investigate the association between miR-146a/HDAC2 and their regulatory roles on the PI3K expression during pancreatitis.

Methods: Rat pancreatic AR42J cells were treated with LPS for simulating pancreatitis. Expression levels of inflammatory factors (IL-6, TNF-α) and miR-146a were detected to determine the optimal LPS concentration for establishing an in vitro pancreatitis model. Cell proliferation and apoptosis were analyzed using CCK-8 and flow cytometry. Immunofluorescence was performed to assess co-localization of HDAC2 and PI3K. ELISA quantified TNF-α and IL-6 levels in cell supernatants. A dual-luciferase assay verified the targeting relationship between miR-146a and HDAC2.

Results: Compared to controls, the cell proliferation ability of the pancreatitis model group was decreased, whereas TSA and miR-146a mimic interventions restored proliferation. The expression of IL-6 and TNF-αin the LPS group was higher than that in the control group, and their expression decreases in the TSA and miR-146a mimic intervention group. Besides the dual luciferase detected the targeting relationship between miR-146a and HDAC2, the immunofluorescence showed co-localization of HDAC2 and PI3K.

Conclusions: TSA and miR-146a mimic enhance proliferation and reduce inflammation in pancreatitis cells. The miR-146a/HDAC2 axis may mediate therapeutic effects in pancreatitis by modulating the PI3K expression.

Keywords: Chronic pancreatitis; HDAC2; Histone deacetylase; PI3K; microRNA 146a.