PARVB promotes malignant melanoma progression and is enhanced by hypoxic conditions

Transl Oncol. 2024 Apr:42:101861. doi: 10.1016/j.tranon.2023.101861. Epub 2024 Feb 1.

Abstract

Beta-Parvin (PARVB) is an actin-binding protein with functionality in extracellular matrix binding. Recent studies suggest its potential as a biomarker for various cancers, given its role in governing several malignancies. Yet, its involvement and modulatory mechanisms in malignant melanoma remain under-explored. In this research, we undertook a comprehensive pan-cancer analysis centered on PARVB. We probed its aberrant expression and prognostic implications, and assessed correlations between PARVB expression and immunocyte infiltration. This expression was subsequently corroborated using clinical samples. Both in vitro and in vivo, we discerned the functional ramifications of PARVB on melanoma. Furthermore, we scrutinized how HIF-1α/2α modulates PARVB and initiated a preliminary investigation into potential downstream pathways influenced by PARVB. Our results illuminate that elevated PARVB expression manifests across various tumors and significantly influences the prognosis of multiple cancers, emphasizing its peculiar expression and prognostic relevance in melanoma. Augmented PARVB levels were inversely proportional to immunocyte penetration in melanoma. Silencing PARVB curtailed cellular proliferation, migration, and invasion in vitro and decelerated tumor expansion in vivo. Notably, hypoxic conditions, triggering HIF-1α/2α activation, appear to elevate PARVB expression by anchoring to the hypoxia-specific responsive element within the PARVB promoter. Enhanced PARVB levels seem intertwined with the activation of cellular proliferation circuits and the damping of inflammatory trajectories. Collectively, these revelations posit PARVB as a potential prognostic indicator and therapeutic linchpin for malignant melanoma.

Keywords: Cell proliferation; Hypoxia; Melanoma; PARVB; Prognosis.