Abstract
Aberrant microRNA (miRNA) expression is a central hallmark of hepatocellular carcinoma (HCC) and identification of the mechanisms underlying the miRNA actions should provide invaluable resource for revealing the molecular basis of different malignant behaviors in HCC. Previous high-throughput analysis has identified miR-767-5p as a unique miRNA signature of HCC, but the biological relevance and corresponding molecular basis of miR-767-5p in HCC is still in its infancy. The current study was, therefore, designed to elucidate whether changes in miR-767-5p expression levels affect HCC pathogenesis, and to further identify the putative targets. miR-767-5p expression was observed to be upregulated by ~ 3.7-fold in surgical HCC specimens as compared to that in adjacent normal hepatic tissues, and this up-regulation trend correlated well to disease progression and predicted a poor prognosis in HCC patients. Functionally, miR-767-5p-overexpressing cells had a significantly higher proliferative, migratory, and invasive potential, and exhibited an enhanced anchorage-dependent clonogenesis and a tumor formation potential in vivo. Mechanistically, PMP22, a core component of integral membrane glycoprotein of peripheral nervous system myelin, was further identified as a direct down-stream target of miR-767-5p in HCC cells. Conversely, stable ectopic expression of PMP22 abrogated the promoting effects of miR-767-5p on HCC aggressive phenotype. Collectively, the available data suggest that as a potent oncomiR, miR-767-5p actions along HCC progression are in part mediated by its function as a posttranscriptional repressor of PMP22 signaling.
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Study design: ZL and WL. Study conduct: ZL, GZ, WY, MF, and MX. Data collection: ZL, GZ, WY, MF, MX, and WL. Data analysis: ZL and WL. Data interpretation: ZL and WL. Drafting and submission of manuscript: ZL and WL.
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418_2020_1878_MOESM2_ESM.tif
Immunoblot stained with an anti-PMP22 antibody or a preabsorbed serum in HepG2 cell extracts, or with an anti-PMP22 antibody in mouse tissue extracts (positive control), demonstrating the specificity of the anti-PMP22 antibody (TIF 3743 kb)
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Zhang, L., Geng, Z., Wan, Y. et al. Functional analysis of miR-767-5p during the progression of hepatocellular carcinoma and the clinical relevance of its dysregulation. Histochem Cell Biol 154, 231–243 (2020). https://doi.org/10.1007/s00418-020-01878-6
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DOI: https://doi.org/10.1007/s00418-020-01878-6