Prognostic value and prospective molecular mechanism of miR‑100‑5p in hepatocellular carcinoma: A comprehensive study based on 1,258 samples

Abstract

The prognostic value and molecular mechanism of microRNA-100-5p (miR-100-5p) in hepatocellular carcinoma (HCC) are still unclear. To explore the prognostic value and the mechanism of miR-100-5p in HCC, the present study analyzed the results of 18 previous studies and bioinformatic datasets. The clinical significance of miR-100-5p and its targets in HCC were investigated using The Cancer Genome Atlas and the Gene Expression Omnibus, as well as relevant literature. In total, 12 online tools were used to predict the target genes of miR-100-5p. Bioinformatics analysis and Spearman correlation analysis were performed, and genomic alterations of the hub genes were evaluated. A meta-analysis with 1,258 samples revealed that miR-100-5p was significantly downregulated in HCC [standard mean difference (SMD), −0.94; 95% confidence interval (CI), −1.14 to −0.74; I2, 35.2%]. Lower miR-100-5p expression was associated with poorer clinical characteristics and a poorer prognosis for patients with HCC. Additionally, bioinformatics analysis revealed that the ‘regulation of transcription’, ‘chromatin remodeling complex’, ‘transcription regulator activity’, ‘pathways in cancer’ and ‘heparan sulfate biosynthesis’ were the most enriched terms. Furthermore, expression of histone deacetylase (HDAC)2, HDAC3, SHC-transforming protein 1 (SHC1), Ras-related protein Rac1 (RAC1) and E3 ubiquitin-protein ligase CBL (CBL) was negatively correlated with miR-100-5p expression. Among these, upregulated HDAC2 [hazard ratio (HR), 1.910; 95% CI, 1.309–2.787; P=0.0007], HDAC3 (HR, 1.474; 95% CI, 1.012–2.146; P=0.0435), SHC1 (HR, 1.52; 95% CI, 1.043–2.215; P=0.0281) and RAC1 (HR, 1.817; 95% CI, 1.248–2.645; P=0.0022) were associated with shorter survival. Alterations in HDAC2, SHC1, RAC1 and IGF1R were linked with a poorer outcome for HCC, and alternative splicing of SHC and RAC1 were significantly decreased and increased in HCC, respectively. In summary, the downregulation of miR-100-5p may be involved in the progression and prognosis of HCC. The upregulation of HDAC2, HDAC3, SHC1 and RAC1 may indicate a poorer survival rate for patients with HCC. Thus, miR-100-5p and these 4 potential target genes may provide novel therapeutic targets and prognostic predictors for patients with HCC.

Angiogenesis-Related Immune Signatures Correlate With Prognosis, Tumor Microenvironment, and Therapeutic Sensitivity in Hepatocellular Carcinoma

“…Previous studies have reported expression levels of BIRC5 ( Jin et al, 2015 ), KITLG ( Hu et al, 2021 ), SPP1 ( Long et al, 2018 ), and SHC1 ( He et al, 2019 ) could serve as biomarkers for predicting prognosis in HCC. BIRC5 is essential for cell division and death and promotes the progression of HCC ( Wheatley and Altieri, 2019 ).…”

miR-100-5p Downregulates mTOR to Suppress the Proliferation, Migration, and Invasion of Prostate Cancer Cells

“…Some studies have found that miR-100-5p inhibits the proliferation, migration and invasion of tumor cells and thebiological behaviors of tumors (21,22). To further study the effects of miR-100-5p on the proliferation, invasion and migration of PCa cells, we transfected miR-100-5p mimics into PCa cells by lipofection and successfully upregulated the expression of miR-100-5p in these cells.…”

“…With an increasingly aging population and changes in diet, the incidence of prostate cancer in Asia is increasing year by year (2). MicroRNAs (miRNAs) are highly conserved noncoding single-stranded RNAs consisting of [21][22][23][24] nucleotides that regulate the expression of target genes through complete or incomplete complementarity binding with target genes and play an important role in the gene regulatory network (3,4). Recent studies have found that miRNAs, as oncogenes or tumor suppressor genes, play an important role in the development and progression of malignant tumors (5).…”

microRNAs Mediated Regulation of the Ribosomal Proteins and its Consequences on the Global Translation of Proteins

“…The third, fourth and fifth miRNAs in the list are miR-100-5p, miR-615-3p and miR-484, respectively: oncogenic miR-100-5p is a potent regulator of viability, metastasis and apoptosis of different cancer types, blocking of miR-100-5p induces apoptosis and prevents the re-emergence of prostate cancer [ 169 ], renal cell carcinoma (RCC) [ 170 ], oral cancer [ 171 ] and NSCLC [ 172 ]. It could also be used as a prognostic marker for HCC [ 173 ], abeta-induced pathologies [ 174 ] and hidradenitis suppurativa [ 175 ]. While, miR-615-3p plays important role in the differentiation of cells, it suppresses GDF5 and FOXO1 and inhibits osteogenesis in the lumbar ligamentum flavum cells [ 269 ], it is also known to have a feed-forward loop with HOXC5, and repress hTERT during the differentiation of cells [ 270 ].…”