PUM1 Promotes HCC Cell Proliferation and Inhibits Mitochondria‑mediated Apoptosis, Accompanied by Activation of the PI3K–AKT Pathway

Junhao Liu,1,2,* Kejun Liu,1,2,* Yongxue Lv,3 Yang Bu,1,2 Peng Yuan1,21Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 2School of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 3School of Basic Medicine, Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yang Bu; Peng Yuan, Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China, Email [email protected]; [email protected]: Belonging to the RNA-binding protein family, Pumilio RNA binding family member 1 (PUM1) modulates gene expression post-transcriptionally through the recognition of particular motifs within the 3′ untranslated region of its target transcripts. The present investigation seeks to elucidate PUM1’s contribution to HCC pathogenesis and advancement, while also probing the molecular mechanisms that underpin its function.Methods: Publicly available datasets were employed to examine PUM1 transcript abundance in hepatocellular carcinoma, along with its relationship to clinicopathological parameters and prognostic outcomes. PUM1 protein levels were subsequently corroborated in clinical HCC specimens via immunoblotting and immunohistochemical staining. To explore the biological functions of PUM1, we established HCCLM3 cell lines with PUM1 overexpression and knockdown. We then evaluated proliferation via EdU, colony formation, and CCK‑8 assays; apoptosis via TUNEL and flow cytometry; mitochondrial membrane integrity and calcium balance using JC‑1, Mito‑Tracker, and Rhod‑2; and oxygen species (ROS) accumulation via MitoSOX and DCFH‑DA. The downstream molecular pathways were further examined by Western blotting.Results: HCC tissues exhibit markedly upregulated PUM1 levels, a feature tightly correlated with poor prognosis. In vitro, PUM1 preserved mitochondrial membrane integrity and calcium homeostasis in HCC cells, while suppressing the accumulation of reactive oxygen species (ROS). Additionally, PUM1 inhibited programmed cell death and promoted cell proliferation. These biological activities were closely associated with the PI3K–AKT signaling pathway. Conversely, knockdown of PUM1 significantly impaired HCC cell proliferation and induced apoptosis.Conclusion: PUM1 promotes HCC cell proliferation and suppresses mitochondria‑mediated apoptosis, effects that are closely associated with activation of the PI3K–AKT pathway.Keywords: pumilio RNA-binding family member 1, hepatocellular carcinoma, proliferation, apoptosis, mitochondrial homeostasis