m6A Modification-Mediated DUXAP8 Regulation of Malignant Phenotype and Chemotherapy Resistance of Hepatocellular Carcinoma Through miR-584-5p/MAPK1/ERK Pathway Axis

Abstract

Hepatocellular carcinoma (HCC) has a poor prognosis due to its high malignancy, rapid disease progression, and the presence of chemotherapy resistance. Long-stranded non-coding RNAs (lncRNAs) affect many malignant tumors, including HCC. However, their mechanism of action in HCC remains unclear. This study aimed to clarify the role of <i>DUXAP8</i> in regulating the malignant phenotype and chemotherapy resistance in HCC. Using an <i>in vivo</i> xenograft tumor model, the regulatory functions and mechanisms of lncRNA <i>DUXAP8</i> in the progression and response of HCC to chemotherapy were explored. It was found that <i>DUXAP8</i> was significantly upregulated in a patient-derived xenograft tumor model based on sorafenib treatment, which is usually associated with a relatively poor prognosis in patients. In HCC, <i>DUXAP8</i> maintained its upregulation in the expression by increasing the stability of m6A methylation-mediated RNA. <i>DUXAP8</i> levels were positively correlated with the proliferation, migration, invasion, and chemotherapy resistance of HCC <i>in vivo</i> and <i>in vitro</i>. In the mechanistic study, it was found that <i>DUXAP8</i> competitively binds to miR-584-5p through a competing endogenous RNA (ceRNA) mechanism, thus acting as a molecular sponge for miR-584-5p to regulate <i>MAPK1</i> expression, which in turn activates the <i>MAPK/ERK</i> pathway. These findings can provide ideas for finding new prognostic indicators and therapeutic targets for patients with HCC.