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沉默富含脯氨酸的卷曲螺旋蛋白2C可抑制肝癌细胞的增殖和转移。

Silencing proline-rich coiled-coil 2C inhibit the proliferation and metastasis of liver cancer cells.

作者信息

Zhang Kai, Xu Jiaming, Chen Ran

机构信息

Department of Oncology Surgery, Yuebei People's Hospital Affiliated to Shantou University Medical College, Shaoguan, China.

Department of Gynaecology, Yuebei People's Hospital Affiliated to Shantou University Medical College, Shaoguan, China.

出版信息

J Gastrointest Oncol. 2023 Feb 28;14(1):287-301. doi: 10.21037/jgo-23-10.

DOI:10.21037/jgo-23-10
PMID:36915448
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10007939/
Abstract

BACKGROUND

Proline-rich coiled-coil 2C () is located in the chromosome region lq where hepatocellular carcinoma (HCC) frequently undergoes genomic fragment amplification, but its role in HCC is unknown. In this study, we aimed to explore the correlation of with HCC diagnosis and progression, as well as its influence on the biological behavior of HCC cells.

METHODS

The Cancer Genome Atlas (TCGA) RNA-sequencing datasets of 371 cases of primary liver cancer and 50 normal liver tissue specimens were obtained to analyze correlation between expression and HCC staging, grades, and overall survival. After confirming expression of in HCC cells, silencing was performed. cell counting, cell clone formation, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and Flow cytometry were used to detect the cell proliferation and apoptosis; wound healing and Transwell assays were used to detect the invasion abilities of cells. Xenograft transplantation in nude mice was performed to investigate the impact of knockdown on tumorigenic capabilities. In addition, the expression levels of EMT (epithelial-mesenchymal transition)-related genes, including E-cadherin, N-cadherin, Twistl, Snail, Slug, and Smad2/3/4, were detected.

RESULTS

Analysis of TCGA data sets revealed that patients with high expression had significantly shorter overall survival. was abundantly expressed in four human hepatocarcinoma cell lines. After knockdown , the proliferation of HCC cells were suppressed and the numbers of apoptotic cells increased. Migration and invasion ability of HCC cells were inhibited by knockdown. Meanwhile, silencing inhibited the tumor formation (indicated by reduced tumor volume and weight compared to the control group) in BALB/c (Bagg Albino Laboratory-bred strain) nude mice. The expressions of EMT-related genes N-cadherin and Vimentin were significantly lower in the knockdown group than in the control group.

CONCLUSIONS

promotes the proliferation and metastasis of liver cancer cells and inhibited apoptosis, potentially through upregulation of EMT related N-cadherin and Vimentin.

摘要

背景

富含脯氨酸的卷曲螺旋蛋白2C()位于染色体1q区域,肝细胞癌(HCC)在此区域常发生基因组片段扩增,但其在HCC中的作用尚不清楚。在本研究中,我们旨在探讨与HCC诊断和进展的相关性,以及其对HCC细胞生物学行为的影响。

方法

获取癌症基因组图谱(TCGA)中371例原发性肝癌和50例正常肝组织标本的RNA测序数据集,以分析表达与HCC分期、分级和总生存期之间的相关性。在确认在HCC细胞中的表达后,进行沉默。采用细胞计数、细胞克隆形成、MTT(3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐)法和流式细胞术检测细胞增殖和凋亡;采用伤口愈合实验和Transwell实验检测细胞的侵袭能力。进行裸鼠异种移植实验,以研究敲低对致瘤能力的影响。此外,检测上皮-间质转化(EMT)相关基因的表达水平,包括E-钙黏蛋白、N-钙黏蛋白、Twist1、Snail、Slug和Smad2/3/4。

结果

对TCGA数据集的分析显示,高表达患者的总生存期显著缩短。在四种人肝癌细胞系中大量表达。敲低后,HCC细胞的增殖受到抑制,凋亡细胞数量增加。敲低抑制了HCC细胞的迁移和侵袭能力。同时,沉默抑制了BALB/c(白化近交系小鼠)裸鼠中的肿瘤形成(与对照组相比,肿瘤体积和重量减小)。敲低组中EMT相关基因N-钙黏蛋白和波形蛋白的表达明显低于对照组。

结论

可能通过上调EMT相关的N-钙黏蛋白和波形蛋白促进肝癌细胞的增殖和转移并抑制凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91fe/10007939/2c08f47e0498/jgo-14-01-287-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91fe/10007939/94d675f6f3a1/jgo-14-01-287-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91fe/10007939/35d4e6c8e2d0/jgo-14-01-287-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91fe/10007939/0adf3a8f501b/jgo-14-01-287-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91fe/10007939/2dd3518809cb/jgo-14-01-287-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91fe/10007939/2c08f47e0498/jgo-14-01-287-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91fe/10007939/94d675f6f3a1/jgo-14-01-287-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91fe/10007939/35d4e6c8e2d0/jgo-14-01-287-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91fe/10007939/0adf3a8f501b/jgo-14-01-287-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91fe/10007939/2dd3518809cb/jgo-14-01-287-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91fe/10007939/2c08f47e0498/jgo-14-01-287-f5.jpg

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