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肝细胞癌中SCAMP3表达及相关基因调控的生物信息学分析与RNA测序

Bioinformatics Analysis and RNA-Sequencing of SCAMP3 Expression and Correlated Gene Regulation in Hepatocellular Carcinoma.

作者信息

Han Shan-Shan, Feng Zhi-Qiang, Liu Rui, Ye Jun, Cheng Wei-Wei, Bao Jun-Bo

机构信息

Beijing Chaoyang Emergency Medical Center, Department of General Surgery, Chaoyang, Beijing 100020, People's Republic of China.

Medical University of Anhui Air Force Clinical School, Department of Hepatobiliary Surgery, Beijing 100142, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Feb 4;13:1047-1057. doi: 10.2147/OTT.S221785. eCollection 2020.

Abstract

BACKGROUND

Secretory Carrier Membrane Proteins 3 (SCAMP3) is a transmembrane protein that affects intracellular trafficking, protein sorting and vesicle formation. Overexpression of SCAMP3 correlates with poorly differentiated hepatocellular carcinoma (HCC). However, the expression and corresponding gene regulation of SCAMP3 in HCC remain unclear.

METHODS

Bioinformatics analyses of clinical parameters and survival data were conducted to predict the prognostic value of SCAMP3 in HCC. RNA sequencing and real-time PCR were conducted to confirm the SCAMP3 expression in HCC tissue. Expression was analyzed using Oncomine and UALCAN, while SCAMP3 alterations and survival analysis were identified by cBioPortal. Differential gene expression with SCAMP3 was analyzed by LinkedOmics and GEPIA. The target networks of enzymes and co-transcriptional factors were identified using Gene enrichment analysis. Expression of SCAMP3 in HCC tissue was detected by RNA-sequencing and Western-blotting.

RESULTS

Based on bioinformatics analysis and detection of mRNA expression, SCAMP3 was over-expressed in numerous tumors, especially in HCC. SCAMP3 level was positively correlated with disease stages and tumor grades and negatively correlated with patient survival. Furthermore, functional network analysis indicated that SCAMP3 regulated metabolic process and DNA replication through oxidative phosphorylation and chromatin remodeling or Ribosome. SCAMP3 regulated a number of gene expressions including PPAP2B, SNRK, ARID4A, PRCC, VPS72 via protein binding and proteasome, which may affect cell adhesion, proliferation, transcription, cell cycle and metabolism. Further, Real-time PCR and Western-blotting showed that the SCAMP3 level was increased in HCC tissue.

CONCLUSION

The present data analysis efficiently reveals information about SCAMP3 expression and correlated function in HCC, laying a foundation for further study of SCAMP3 in the tumor.

摘要

背景

分泌载体膜蛋白3(SCAMP3)是一种跨膜蛋白,影响细胞内运输、蛋白质分选和囊泡形成。SCAMP3的过表达与低分化肝细胞癌(HCC)相关。然而,SCAMP3在HCC中的表达及相应的基因调控仍不清楚。

方法

对临床参数和生存数据进行生物信息学分析,以预测SCAMP3在HCC中的预后价值。进行RNA测序和实时PCR以确认HCC组织中SCAMP3的表达。使用Oncomine和UALCAN分析表达情况,而通过cBioPortal鉴定SCAMP3的改变和生存分析。通过LinkedOmics和GEPIA分析与SCAMP3的差异基因表达。使用基因富集分析鉴定酶和共转录因子的靶标网络。通过RNA测序和蛋白质印迹法检测HCC组织中SCAMP3的表达。

结果

基于生物信息学分析和mRNA表达检测,SCAMP3在多种肿瘤中过表达,尤其是在HCC中。SCAMP3水平与疾病分期和肿瘤分级呈正相关,与患者生存呈负相关。此外,功能网络分析表明,SCAMP3通过氧化磷酸化、染色质重塑或核糖体调节代谢过程和DNA复制。SCAMP3通过蛋白质结合和蛋白酶体调节包括PPAP2B、SNRK、ARID4A、PRCC、VPS72在内的多种基因表达,这可能影响细胞粘附、增殖、转录、细胞周期和代谢。此外,实时PCR和蛋白质印迹法显示HCC组织中SCAMP3水平升高。

结论

本数据分析有效地揭示了SCAMP3在HCC中的表达及相关功能信息,为进一步研究SCAMP3在肿瘤中的作用奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f2f/7007781/81100ae13c4b/OTT-13-1047-g0001.jpg

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