A complex microRNA regulatory network may control the HCP5/UTP3/c-Myc/VAMP3 signaling axis.

The recently published work by Nan and colleagues 1 Nan Y. Luo Q. Wu X. Chang W. Zhao P. Liu S. Liu Z. HCP5 prevents ubiquitination-mediated UTP3 degradation to inhibit apoptosis by activating c-Myc transcriptional activity. Mol. Ther. 2023; 31: 552-568https://doi.org/10.1016/j.ymthe.2022.10.006 Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar describes the functional impact of the long non-coding RNA (lncRNA) histocompatibility leukocyte antigen complex P5 (HCP5) as an apoptosis inhibitor through the UTP3/c-Myc/VAMP3 signaling axis in esophageal squamous cell carcinoma (ESCC). The authors demonstrated that HCP5 interacts and stabilizes UTP3 small-subunit processome component (UTP3) by affecting E3 ligase tripartite motif containing 29 (TRIM29)-mediated ubiquitination and subsequent proteosome degradation of UTP3. As a consequence, UTP3 recruits the oncogenic transcription factor c-Myc and promotes vesicle-associated membrane protein 3 (VAMP3) expression, which leads to caspase-dependent apoptosis inhibition and chemoresistance. Finally, the authors investigated the HCP5/UTP3/c-Myc/VAMP3 axis in a cohort of 34 patients with ESCC who received neoadjuvant chemoradiotherapy (17 cases with chemosensitivity and 17 with chemoresistance). The members of this signaling axis were overexpressed in the chemoresistant subgroup, and VAMP3 expression was positively correlated with both HCP5 and c-Myc expression.