SPATS2, negatively regulated by miR-145-5p, promotes hepatocellular carcinoma progression through regulating cell cycle

Dong, Gang; Zhang, Shanshan; Shen, Shen; Sun, Lulu; Wang, Xuemei; Li, Ang; Wu, Jie; Liu, Tingting; Wang, Chaoyan; Wang, Huanbin; Lu, Tianlan; Rao, Benchen; Ren, Zhigang

doi:10.1038/s41419-020-03039-y

Cited by 25 publications

(18 citation statements)

References 34 publications

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“… 26 miR-145 was also reported to regulate hepatocellular carcinoma progression and proliferation of epithelial ovarian cancer by targeting SPATS2 and SMAD4. 27 , 28 In order to reveal the relationship between miR-145 and ARF6 in HCC, some further experiments were implemented. ARF6 was subsequently predicted to be a downstream target gene of miR-145 by four different miRNA targeting prediction tools, and the targeting relationship was confirmed through dual-luciferase reporter assay.…”

Section: Discussionmentioning

confidence: 99%

microRNA-145-5p Inhibits Migration, Invasion, and Metastasis in Hepatocellular Carcinoma by Inhibiting ARF6

Wang¹,

Wang²,

Gu³

2021

CMAR

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Purpose Hepatocellular carcinoma (HCC) has the fourth highest rate of mortality among the different types of cancer worldwide. This study aimed to investigate the functions of microRNA-145-5p and AFR6 on migration, invasion and metastasis in HCC. Methods A total of 150 pairs of tumor and their matched adjacent nontumor liver tissues were collected from HCC patients. Expressions of microRNA-145-5p and AFR6 were measured by real-time PCR in HCC tissues and in HCC cell lines. The correlations between microRNA-145-5p and HCC prognosis were investigated. The proliferation, migration, invasion, cell cycle progression, and apoptosis of HCCLM3 cells were evaluated with CCK8, wound healing, transwell, and flow cytometric experiments. Results The expression of miR-145-5p was confirmed to be downregulated not only in HCC tissues but also in several HCC cell lines compared with normal controls. A low expression level of miR-145-5p was notably associated with poor prognosis in patients with HCC and certain characteristics of metastatic tumors. In vitro, miR-145-5p negatively regulated cell proliferation, migration, and invasion and induced apoptosis in HCCLM3 cells. Subsequent experiments further verified that ARF6 is a novel target of miR-145-5p and is significantly overexpressed in HCC tissues. Overexpression of ARF6 circumvented the effects of miR-145-5p in HCCLM3 cells. Conclusion miR-145-5p may play a pivotal role in HCC metastasis via regulating ARF6, and these findings may both provide further insights into the key factors of HCC metastasis and prove to be useful in the development of novel treatment options for HCC.

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Section: Discussionmentioning

confidence: 99%

microRNA-145-5p Inhibits Migration, Invasion, and Metastasis in Hepatocellular Carcinoma by Inhibiting ARF6

Wang¹,

Wang²,

Gu³

2021

CMAR

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“…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 ]. Additionally, SPATS2 serves as a target transcript of the small nucleolar RNA hostgene5 SNHG5 in colorectal cancer cells [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

SPATS2 is positively activated by long noncoding RNA SNHG5 via regulating DNMT3a expression to promote hepatocellular carcinoma progression

Jia

Huang

et al. 2022

PLoS ONE

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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.

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“…For example, miR-30a-5p can inhibit glycolysis and increase sensitivity to sorafenib through targeting CLCF1 in HCC, indicating modulating the expression level of miR-30a-5p has a promising therapeutic effect on HCC patients ( Zhang et al, 2020 ). Meanwhile, miR-145-5p can promote tumor progression by inhibiting SPATS2 ( Dong et al, 2020 ). In view of this research progress, miRNAs attract increasing research interest as potential targets in HCC diagnosis and treatment.…”

Section: Introductionmentioning

confidence: 99%

Expression and Diagnostic Value of miR-497 and miR-1246 in Hepatocellular Carcinoma

Chen

Wen

et al. 2021

Front. Genet.

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ObjectiveSerum microRNAs (miRNAs) may serve as biomarkers in various cancers. Our study aims to explore the roles of miR-497 and miR-1246 in hepatocellular carcinoma (HCC).MethodsThe expression levels of miR-497 and miR-1246 were measured by RT-PCR. A correlation analysis was conducted between the expression levels of miR-497 and miR-1246 and clinicopathological characteristics of patients. The receiver operating characteristic (ROC) curve was applied to evaluate the diagnostic efficacy in HCC. In addition, bioinformatics tools were also utilized to predict the potential targets of miR-497 and miR-1246.ResultsThe expression level of miR-497 in HCC was significantly down-regulated compared with the control group while the miR-1246 revealed a significantly higher expression level in HCC. There was a significant correlation demonstrated between the expression levels of miR-497 and miR-1246 in preoperative serum of HCC and the differentiation degree, Tumor Node Metastasis (TNM) classification, and metastasis. The expression levels of serum miR-497 and miR-1246 were significantly associated with the diagnosis, prognosis, and overall survival rate of patients with HCC. Moreover, the potential target genes of miR-497 in HCC include ARL2, UBE2Q1, PHF19, APLN, CHEK1, CASK, SUCO, CCNE1, and KIF23. The low expression of these nine genes is associated with a better prognosis of HCC patients. AUTS2 is a novel target gene of miR-1246, and its low expression is significantly related to the low overall survival rate of HCC patients.ConclusionsmiR-497 and miR-1246 are possibly involved in the progression of HCC by regulating target genes, respectively, and could serve as biomarkers in HCC.

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SPATS2, negatively regulated by miR-145-5p, promotes hepatocellular carcinoma progression through regulating cell cycle

Cited by 25 publications

References 34 publications

microRNA-145-5p Inhibits Migration, Invasion, and Metastasis in Hepatocellular Carcinoma by Inhibiting ARF6

microRNA-145-5p Inhibits Migration, Invasion, and Metastasis in Hepatocellular Carcinoma by Inhibiting ARF6

SPATS2 is positively activated by long noncoding RNA SNHG5 via regulating DNMT3a expression to promote hepatocellular carcinoma progression

Expression and Diagnostic Value of miR-497 and miR-1246 in Hepatocellular Carcinoma

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