Biostatistics mining associated method identifies AKR1B10 enhancing hepatocellular carcinoma cell growth and degenerated by miR-383-5p

Abstract

Previous studies have reported that the aberrantly expressed AKR1B10 is associated with many cancer development, however the functional roles of AKR1B10 and its regulatory mechanisms in hepatocellular carcinoma (HCC) have been limited studied. In this project, we identified AKR1B10 functional as an oncogene in HCC through tumor/normal human tissue comparison from both GEO microarray and TCGA RNAseq dataset. Further experimental validations from three HCC cell lines (SMMC-7721, HePG2 and HeP3B) also suggested the ontogenetic functions of AKR1B10 in HCC tumor growth. By knocking down AKR1B10 through shRNA in HCC HeP3B cells, we showed it significantly induced cell cycle arrest and inhibited cell growth. Interestingly, integrative analysis of TCGA RNAseq data and miRNA-seq data predicted that miR-383-5p, a novel post-transcriptional tumor suppressor, is negatively associated with AKR1B10 expression. To further investigate the role of miR-383-5p in regulating AKR1B10 in HCC, we performed Dual-luciferase reporter assay experiments. Results showed that miR-383-5p is an upstream modulator targeting AKR1B10 in the post-transcriptional stage. Thus, we report AKR1B10 modulated regulated by miR-383-5p, promotes HCC tumor progress, and could be potentially a therapeutic target for precision medicine in HCC.

Anillin facilitates cell proliferation and induces tumor growth of hepatocellular carcinoma via miR-138/SOX4 axis regulation

“…Antibodies against Anillin and SOX4 and the other related proteins were purchased (Abcam, USA) for the using of the Western blot analysis and immunohistochemistry assay. The methods for the assays above were performed as the same protocol described in we previously research [ 12 ]. Especially, the protein levels obtained from IHC were assigned to two experienced pathologists and examined in blind, then set into two groups as staining intensity graded subjectively: no to low staining (0–1+) and moderate to high staining (2 + ~3+).…”

Pseudogene AKR1B10P1 enhances tumorigenicity and regulates epithelial‐mesenchymal transition in hepatocellular carcinoma via stabilizing SOX4

“…In our previous study, Aldo-Keto Reductase Family 1 Member B10 (AKR1B10) was discovered highly expressed in multiple HCC cells and remarkably promotes cell growth. 15 AKR1B10 pseudogene 1 (AKR1B10P1) is the isoform pseudogene of AKR1B10, exhibiting almost no transcriptional profile in normal hepatocytes. As we observed, AKR1B10P1 emerges a positively correlated expression compatible with its parental gene in HCC cells.…”

Comprehensive Network Analysis Reveals Alternative Splicing-Related lncRNAs in Hepatocellular Carcinoma

“…HCC differentially expressed (DE) lncRNAs and pseudogenes between tumor and normal samples (T/N) were analyzed by R package limma (Smyth, 2005) with a statistical cutoff (p < 1.0E-04 and fold-change > 2). The identification of DE miRNAs had been reported in our previous work (Wang et al, 2018). The identified HCC-specific expressed features (lncRNAs, pseudogenes, and miRNAs) are expected to represent potential key mechanisms in liver neoplasm.…”