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Background: HAUS Augmin-like complex subunit 1(HAUS1), as a controlling gene, which affected the production of spindle was firstly discovered in Drosophila cells. Although HAUS1 has been intensively studied, but its significance and relationship with the immune microenvironment in Hepatocellular carcinoma (HCC) remain unclear. Materials and Methods: All data of HCC in this paper were obtained from The Cancer Genome Atlas(TCGA), Genotype-Tissue Expression (GTEx), Gene Expression Omnibus (GEO) and the Human Protein Atlas(HPA) database. The role and potential value of HAUS1 in the tumorigenesis and development of HCC were studied by applying plenty of bioinformatics analysis methods. Knocked down the expression of HAUS1 through siRNA and further investigated the function of HAUS1 in HCC Results: HAUS1 was highly expressed in HCC, which led to a poor prognosis. ROC curve analysis showed that HAUS1 had a excellent diagnostic value. It was also associated with clinical stage, pathological grade and AFP of HCC. Univariate and multivariate COX regression analysis showed that HAUS1 was an independent prognostic factor for HCC patients. HAUS1 was associated with immune cells infiltrate and immune checkpoints in HCC, and it could generate significative therapeutic results when combined with anti-CTLA4 and anti-CD274 treatment. In vitro experiments, HAUS1 was found to promote the proliferation, invasion and metastasis, participated in cell cycle regulation and inhibited apoptosis of HCC. Conclusion: These results suggested that HAUS1 might serve as a potential therapeutic target, as well as a diagnostic, prognostic, and survival biomarker for HCC.
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RRP12 (ribosomal RNA processing 12 homolog) is a nucleolar protein involved in the maturation and transport of eukaryotic ribosomal subunits and is a type of RNA binding protein. In recent years, considerable research has indicated that RRP12 is associated with the occurrence and development of multiple cancers. However, there is no research on RRP12 in hepatocellular carcinoma. Herein, we aimed to explore the role and significance of RRP12 in hepatocellular carcinoma.We used the TIMER and GEPIA databases to perform pan-cancer analyses of RRP12. The impact of RRP12 on the prognosis was analyzed through the GEPIA database. The relationship between RRP12 and immune cell infiltration was investigated by TIMER and GEPIA databases. Moreover, the expression of RRP12 in various liver cancer cells was evaluated by Western Blot to determine the cell line for the next experiment. Scratch test, Transwell test, and Edu tests were applied to validate the effects of RRP12 on the function of liver cancer cells. And the data were statistically analyzed.Pan-cancer analysis found that RPP12 was significantly upregulated in many cancers. Moreover, the prognostic analysis revealed that the difference in the expression of RRP12 has statistical significance for the overall survival rate and disease-free survival rate of liver cancer patients. In order to analyze the correlation between the expression level of RRP12 and clinical parameters, it was found that there was a significant negative correlation with tumor stage, tumor grade and tumor size. Univariate and multivariate analysis showed that RRP12 could be used as an independent prognostic factor for patients with hepatocellular carcinoma. Cellular experiments have proved that knocking down RRP12 can inhibit the proliferation, invasion, and metastasis of liver cancer cells.Therefore, RRP12 significantly affects the occurrence and development of HCC. Hence, RRP12 can become a potential target and prognostic biomarker for the treatment of hepatocellular carcinoma.
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BACKGROUND: The HSP70 family of heat shock protein plays a critical role in protein synthesis and transport to maintain protein homeostasis. Several studies have indicated that HSP70s are related to the development and occurrence of various cancers. METHODS: The relationship between the overall survival rate of hepatocellular carcinoma patients and the expression of 14 HSP70s from multiple databases, such as TCGA, ONCOMINE, cBioPortal was investigated. Western Blot and PCR were used to evaluate HSPA4 and HSPA14 expressions in various HCC cells to identify suitable cell lines for further experiments .Wound-healing assays, Transwell assays and EdU assays were used to verify the effects of HSPA4 and HSPA14 on the function of hepatocellular carcinoma cells, and statistical analysis was performed. RESULTS: Hepatocellular carcinoma tissues significantly expressed the 14 HSP70s compared to the normal samples. Besides, the high HSPA1A, HSPA1B, HSPA4, HSPA5, HSPA8, HSPA13, and HSPA14 expressions were inversely associated with the overall survival rate of patients, tumor grade, and cancer stage. A PPI regulatory network was constructed using the 14 HSP70s proteins with HSPA5 and HSPA8 at the network center. Univariate and multivariate analyses showed that HSPA4 and HSPA14 could be independent risk factors for the prognosis of hepatocellular carcinoma patients. Cell experiments have also confirmed that reducing HSPA4 and HSPA14 expressions can inhibit the invasion, metastasis, and proliferation of hepatocellular carcinoma cells. CONCLUSIONS: Therefore, the HSP70s significantly influence the occurrence and development of hepatocellular carcinoma. For instance, HSPA4 and HSPA14 can be novel therapeutic targets and prognostic biomarkers for hepatocellular carcinoma.
