Abstract
Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors with high mortality worldwide. Spermatogenesis-associated serine-rich 2 (SPATS2) could be a novel diagnostic and prognostic biomarker in HCC. However, the regulatory mechanism of SPATS2 in HCC requires further elucidation. Therefore, the study’s objective was to investigate this process in HCC. In this study, we found that SPATS2 is significantly upregulated in HepG2 cells to promote cell growth and migration. SPATS2 is the target transcript of lncRNA SNHG5. SPATS2 positively affects the proliferation and migration of HepG2 cells caused by the higher expression of SNHG5. Mechanistically, we identified that the elevated of SPATS2 was attributed to SNHG5 related hypomethylation of SPATS2. SNHG5 reduced the expression of DNMT3a to suppress the methylation level of SPATS2. Taken together, our results uncover a novel epigenetic regulatory mechanism of lncRNA SNHG5-DNMT3a axis-related SPATS2 expression underlying HCC progression. This may serve as a novel prognostic marker and a promising therapeutic target for the treatment of HCC.
Highlights
Hepatocellular carcinoma (HCC) is the sixth most common cancer and one of the greatest threats to human health worldwide [1]
Spermatogenesis-associated serine-rich 2 (SPATS2) expression patterns in patient samples were derived from TCGA database, SPATS2 was more highly expressed in human primary liver cancer tissue (n = 369) than in normal human liver tissue (n = 50) (Fig 1A)
The qRT-PCR results showed that SPATS2 was significantly higher in HCC HepG2 cells than in line HL-7702 (L02) human normal liver cells (Fig 1B)
Summary
Hepatocellular carcinoma (HCC) is the sixth most common cancer and one of the greatest threats to human health worldwide [1]. Despite the rapid developments in therapy, the overall survival rate of patients is still low due to its complex pathogenesis, the heterogeneity of the cancer cells, the high recurrence rate, and resistance to chemotherapy [3]. SPATS2 is dysregulated in a few types of cancers such as HCC, squamous cell carcinoma, and colorectal carcinoma (CRC) [4, 5]. In liver cancer, it is highly expressed and could predict poor prognosis [6]. A recent study indicated that SPATS2 promotes hepatocellular carcinoma progression by regulating the cell cycle [7]. SPATS2 serves as a target transcript of the small nucleolar RNA hostgene SNHG5 in colorectal cancer cells [8].
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