RT Journal Article SR Electronic T1 HCP5 prevents ubiquitination-mediated UTP3 degradation to inhibit apoptosis by activating c-Myc transcriptional activity JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.06.13.495862 DO 10.1101/2022.06.13.495862 A1 Yabing Nan A1 Qingyu Luo A1 Xiaowei Wu A1 Wan Chang A1 Pengfei Zhao A1 Shi Liu A1 Zhihua Liu YR 2022 UL http://biorxiv.org/content/early/2022/06/15/2022.06.13.495862.abstract AB Inducing cancer cell apoptosis through cytotoxic reagents is the main therapeutic strategy for diverse cancer types. However, several antiapoptotic factors impede curative cancer therapy by driving cancer cells to resist cytotoxic agent-induced apoptosis, thus leading to refractoriness and relapse. To define critical antiapoptotic factors that contribute to chemoresistance in esophageal squamous cell carcinoma (ESCC), we generated two pairs of parental and apoptosis-resistant cell models through cisplatin (DDP) induction and then performed whole-transcriptome sequencing. We identified the long noncoding RNA (lncRNA) histocompatibility leukocyte antigen complex P5 (HCP5) as the chief culprit for chemoresistance. Mechanistically, HCP5 interacts with UTP3 small subunit processome component (UTP3) and prevents UTP3 degradation from E3 ligase tripartite motif containing 29 (TRIM29)-mediated ubiquitination. UTP3 then recruits c-Myc to activate vesicle-associated membrane protein 3 (VAMP3) expression. Activated VAMP3 suppresses caspase-dependent apoptosis and eventually leads to chemoresistance. Accordingly, the expression level of the HCP5/UTP3/c-Myc/VAMP3 axis in chemoresistant patients is significantly higher than that in chemosensitive patients. Thus, our study demonstrated that the HCP5/UTP3/c-Myc/VAMP3 axis plays an important role in the inhibition of cancer cell apoptosis and that HCP5 can be a promising chemosensitive target for cancer treatment.Competing Interest StatementThe authors have declared no competing interest.