TPX2 silencing exerts anti‑tumor effects on hepatocellular carcinoma by regulating the PI3K/AKT signaling pathway

Abstract

Hepatocellular carcinoma (Hcc) is one of the primary causes of cancer-associated deaths worldwide. current treatment methods include surgical resection, chemotherapy and radiotherapy; however the curative rate remains low, thus novel treatments are required. The aim of the present study was to investigate the role of targeting protein for Xenopus kinesin-like protein 2 (TPX2) in the growth of Hcc and its underlying molecular mechanism. Immunohistochemistry staining, reverse transcription-quantitative (RT-q)PcR and western blotting were used to detect the expression of TPX2 mRNA and protein in liver cancer tissue samples, adjacent normal liver tissue samples, and the Hcc cell lines Huh7, Hep3B, PLc/PRF/5 and MHcc97-H. The recombinant plasmid pMagic4.1-shRNA-TPX2 was constructed and transfected into Huh7 and Hep3B Hcc cells to silence TPX2 expression. The proliferation, apoptosis, migration and invasion of Huh7 cells and Hep3B cells were evaluated before and after TPX2 silencing. The mRNA and protein expression levels of multiple signaling pathway-associated genes were detected by RT-qPcR and western blotting. The expression levels of TPX2 mRNA and protein were significantly higher in Hcc tissue samples compared with adjacent normal liver tissue sample. TPX2 mRNA and protein expression levels were detected in the different Hcc cell lines. The recombinant plasmid pMagic4.1-shRNA-TPX2 was successfully transfected into Huh7 and Hep3B cells, resulting in TPX2 silencing. TPX2 knockdown significantly reduced cell proliferation, cell migration and cell invasion of Huh7 and Hep3B cells, whilst also increasing the rate of apoptosis in these cells. Following TPX2 silencing, the expression levels of PI3K, phospho-AKT, Bcl-2, c-Myc and Cyclin D1 were significantly decreased, whereas the expression levels of P21 and P27 were significantly increased. In conclusion, TPX2 may suppress the growth of Hcc by regulating the PI3K/AKT signaling pathway and thus, TPX2 may be a potential target for the treatment of liver cancer.

<p>Long Non-Coding RNA NRAD1 and LINC00152 are Highly Expressed and Associated with Prognosis in Patients with Hepatocellular Carcinoma</p>

“…[1][2][3] Researchers exerted efforts to determine the potential genes contribution to hepatocellular carcinoma and to understand the molecular mechanism of gene expression regulation in developing novel diagnostic and therapeutic biomarkers. [4][5][6] During recent decades, long non-coding RNA (lncRNA) is the popular research field, which is a type of non-coding RNA with a length varying from 200nt to 100kb. Widely presenting in nuclei and cytoplasm, lncRNA is rarely involved in protein-coding regulation due to the lack of open reading frame.…”

Screening and Identification of Potential Biomarkers in Hepatitis B Virus-Related Hepatocellular Carcinoma by Bioinformatics Analysis

“…Moreover, it was observed that knocking down TPX2 in hepatocarcinoma cell lines effectively reduced cell growth via G2/M blockage and induced apoptosis (Hsu et al, 2017). TPX2 has also been reported to promote HCC development by activating PI3K/Akt signal (Huang et al, 2019).…”

Identification and Validation of a Reliable Prognostic Eleven-Genes Signature for Hepatocellular Carcinoma

“…Liu et al found that siRNA-mediated knockdown of TPX2 suppressed HCC cell invasion via inactivating AKT signaling and down-regulation of MMP2 and MMP9 expression in SMMC-7721 and HepG2 cells [46]. Another study reported that the siRNA-mediated knockdown of TPX2 may suppress the growth of HCC by regulating the PI3K/AKT signaling pathway [47].…”