Decoding the Versatile Landscape of Autophagic Protein VMP1 in Cancer: A Comprehensive Review across Tissue Types and Regulatory Mechanisms

Abstract

Autophagy, a catabolic process orchestrating the degradation of proteins and organelles within lysosomes, is pivotal for maintaining cellular homeostasis. However, its dual role in cancer involves preventing malignant transformation while fostering progression and therapy resistance. Vacuole Membrane Protein 1 (VMP1) is an essential autophagic protein whose expression, per se, triggers autophagy, being present in the whole autophagic flux. In pancreatic cancer, VMP1—whose expression is linked to the Kirsten Rat Sarcoma Virus (KRAS) oncogene—significantly contributes to disease promotion, progression, and chemotherapy resistance. This investigation extends to breast cancer, colon cancer, hepatocellular carcinoma, and more, highlighting VMP1’s nuanced nature, contingent on specific tissue contexts. The examination of VMP1’s interactions with micro-ribonucleic acids (miRNAs), including miR-21, miR-210, and miR-124, enhances our understanding of its regulatory network in cancer. Additionally, this article discusses VMP1 gene fusions, especially with ribosomal protein S6 kinase B1 (RPS6KB1), shedding light on potential implications for tumor malignancy. By deciphering the molecular mechanisms linking VMP1 to cancer progression, this exploration paves the way for innovative therapeutic strategies to disrupt these pathways and potentially improve treatment outcomes.

The Multifaceted Role of miR-21 in Pancreatic Cancers

“…The studies identified several autophagy-related miRNAs as potential prognostic biomarkers, therapeutic targets, and even delivery vehicles to increase chemosensitivity in pancreatic cancer by modulating autophagy; however, the direct role of miR-21 as a modulator of autophagy in pancreatic cancer remains unknown. A very recent article has discussed the role of Vacuole Membrane Protein 1 (VMP1) [ 104 , 105 , 106 , 107 ] an essential autophagic protein, and its relation to miR-21-mediated regulation [ 107 ]. Research has shown that miR-21 originates from a primary transcript located near the 3′-untranslated region of the VMP1 gene, further, the VMP1-miR-21 fusion transcript gets processed by Drosha, releasing mature miR-21 and the VMP1 mRNA transcript [ 106 ].…”

VMP1: a multifaceted regulator of cellular homeostasis with implications in disease pathology

“…In contrast, in hepatocellular carcinoma, VMP1 exerts a protective role by decreasing tumor spread and improving patient prognosis ( Ying et al, 2011 ; Guo et al, 2012 ). Amirfallah et al (2019) observed elevated VMP1 expression in breast tumors, and VMP1’s potential fusion with the ribosomal protein S6 kinase- 70 kDa polypeptide 1, also known as RPS6KB1 gene, suggesting a role for VMP1 in the development of malignant tumors ( Renna et al, 2024 ). However, in breast ( Amirfallah et al, 2019 ; Park et al, 2023 ), colorectal ( Qian et al, 2014 ; Guo et al, 2015 ; Wang et al, 2020a ), gastric ( Wang et al, 2021a ; Wu et al, 2023 ), esophageal, and ovarian cancers ( Liu et al, 2014 ; Zheng et al, 2016 ), the relationship between VMP1 expression and malignancy is less clear, with conflicting reports that underscore the necessity for further investigation into the genetic context of each tumor type ( Renna et al, 2024 ).…”