CD39 Contributes to the Ability of Cell Invasion in Heterogeneity of Colorectal Cancer

Xiaosong Li, Yifen Shen, Jianhua Lang, Jianzhong Wu, Zhenhai Qian, Genhai Shen, Yihang Shen
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Abstract

Tumour heterogeneity will accumulate and amplify during cell culture and passage, even if derived from the same strain. In the current study, multiple batches of colorectal cancer HCT116 and HT29 cell lines were obtained using different conditions of trypsin digestion and processed for RNA sequencing. CD39 was identified as a biomarker highly expressed in easily trypsin-digested cells compared to the undigestible ones. Furthermore, CD39 was determined to enhance cell invasion and suppress cell apoptosis but not affect cell proliferation. Moreover, CD39 could activate the TGF-β/SMAD3 signalling pathway, whereas the expression of CD39 was negatively regulated by SMAD3 via recruitment of SETDB1 and adding H3K9me3 to the CD39 promoter in HCT116 cells. Overall, our study uncovered distinct gene signatures amongst different heterogeneities of colorectal cells and revealed the effect of CD39 on cell invasion and apoptosis, as well as determined the epigenetic role in regulating CD39 transcription.

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CD39参与结直肠癌异质性的细胞侵袭能力
在细胞培养和传代过程中,即使来自同一菌株,肿瘤异质性也会累积和扩增。本研究采用不同的胰蛋白酶消化条件,获得多批结直肠癌HCT116和HT29细胞系,并进行RNA测序处理。与不易消化的细胞相比,CD39在易胰蛋白酶消化的细胞中被鉴定为高表达的生物标志物。此外,CD39增强细胞侵袭和抑制细胞凋亡,但不影响细胞增殖。此外,CD39可以激活TGF-β/SMAD3信号通路,而在HCT116细胞中,SMAD3通过募集SETDB1和将H3K9me3添加到CD39启动子中来负向调节CD39的表达。总的来说,我们的研究揭示了不同异质性结肠直肠癌细胞的不同基因特征,揭示了CD39对细胞侵袭和凋亡的影响,并确定了CD39转录调控的表观遗传学作用。
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期刊介绍: The Journal of Cellular and Molecular Medicine serves as a bridge between physiology and cellular medicine, as well as molecular biology and molecular therapeutics. With a 20-year history, the journal adopts an interdisciplinary approach to showcase innovative discoveries. It publishes research aimed at advancing the collective understanding of the cellular and molecular mechanisms underlying diseases. The journal emphasizes translational studies that translate this knowledge into therapeutic strategies. Being fully open access, the journal is accessible to all readers.
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