Role of KCNQ1OT1 / miR-27b-5p in Modulating Dihydrolipoamide S-acetyltransferase (DLAT): Insights into Cuproptosis in Hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) poses a significant global health challenge due to late diagnosis and limited treatment effectiveness. Cuproptosis, a newly identified form of copper-induced mitochondrial cell death, is emerging as a promising therapeutic target, with Dihydrolipoamide S-acetyltransferase (DLAT) playing a key role in protein aggregation during this process. This study investigates the long non-coding RNA KCNQ1OT1/miR-27b-5p/DLAT regulatory axis’ involvement in cuproptosis and HCC progression, emphasizing its potential for diagnostic and therapeutic monitoring. Accordingly, a total of 180 participants were divided into three main groups: A healthy control group, untreated HCC group (naïve, NV) and treated HCC group which further subclassified into HCC patients treated with Sorafenib (Sor) or treated with Regorafenib (Rog). The regulatory axis KCNQ1OT1/miR-27b-5p/DLAT was predicted through bioinformatics analysis. Expression levels of KCNQ1OT1, miR-27b-5p, and cuproptosis-related genes (ATP7A, ATP7B, SLC31A1) were assessed using RT-qPCR. Serum DLAT was measured through ELISA technique. The NV group showed elevated serum DLAT levels, KCNQ1OT1 expression, and ATP7A/B levels, while miR-27b-5p, SLC31A1 expression, and serum Glutathione (GSH) levels were reduced, indicating impaired cuproptosis. In contrast, the treated groups (Sor & Rog) demonstrated lower DLAT, KCNQ1OT1, and ATP7A/B levels, alongside higher miR-27b-5p, SLC31A1, and GSH levels, suggesting copper accumulation and activated cuproptosis. ROC and correlation analyses indicate that KCNQ1OT1, miR-27b-5p, and DLAT constitute a regulatory axis, potentially serving as diagnostic and therapeutic monitoring biomarkers in HCC.