Hepatocellular carcinoma (HCC) is the sixth most common neoplasm and the third leading cause of cancer-related deaths worldwide. Although great progress has been made in treatment strategies, such as surgical resection, trans-arterial chemoembolization, radiofrequency ablation, and liver transplantation, the five-year survival rate of HCC is less than 10%. The poor prognosis of HCC is mainly due to the diagnosis at late stage and its recurrence potential. Thus, it is of great importance to further explore the mechanisms of HCC progression and identify novel HCC diagnostic markers.
Spermatogenesis associated serine rich 2 (SPATS2) has been reported to contribute to the tumorigenesis of multiple malignancies. The molecular function of SPATS2 in hepatocellular carcinoma (HCC) is still not fully understood.
Researchers from the First Affiliated Hospital of Zhengzhou University investigated the expression pattern and function roles of SPATS2 in HCC, and also explored the regulation of SPATS2 expression.
To determine the expression profile of SPATS2 in most common cancers, Pan-cancer analysis was performed based on TCGA and GTEX databases. We found SPATS2 mRNA expression was frequently upregulated in most cancers. We further validated the expression of SPATS2 in TCGA and the GEO database by bioinformatics analysis.
To better understand the role of SPATS2 in HCC, they examined the expression of SPATS2 in different HCC cell lines. The expression of SPATS2 was significantly upregulated in four HCC cell lines (HepG2, SK-Hep-3b, MHCC97-H, and SMMC-7721) in comparison with normal cell lines. HepG2 and SMMC-7721, which had relatively higher SPATS2 expression, were selected for subsequent experiments.
They performed loss-of-function studies using shRNAs targeting SPATS2 and the RNA silence efficiency was determined by western blot. The subcutaneous xenotransplanted and orthotopic implanted tumor models were employed to further investigate the function of SPATS2 on HCC proliferation in vivo.
To further explore the biological function of SPATS2 in HCC, comprehensive bioinformatics analysis was performed using TCGA HCC datasets. The results showed that cell cycle related pathways were significant activated in SPATS2-high HCC tissues compared with those in non-malignant tissues.
They found that SPATS2 was highly expressed in HCC tissues in comparison with that in adjacent normal tissues. High expression of SPATS2 was associated with vascular invasion, advanced TNM stages, tumor multiplicity, and poor survival.
Functionally, SPATS2 was found to promote the proliferation and metastasis of HCC cells both in vitro and in vivo, while knockdown of SPATS2 enhanced apoptosis and G1 arrest of HCC cells in vitro. Mechanistically, bioinformatics analysis revealed that MiR-145-5p directly targeted SPATS2 and functional rescue experiments verified that MiR-145-5p overexpression could abolish the effect of SPATS2 on the regulation of HCC malignant phenotype.
Taken together, their findings suggest that SPATS2 functions as an oncogene in HCC. The MiR-145-5p/SPATS2 axis provides a novel mechanism underlying HCC progression and may serve as a potential therapeutic target for HCC. This study has been published in Cell Death & Disease recently.
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