Enterobacterial LPS-inducible LINC00152 is regulated by histone lactylation and promotes cancer cells invasion and migration.
Enterobacterial LPS-inducible LINC00152 is regulated by histone lactylation and promotes cancer cells invasion and migration.
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肠杆菌 LPS 诱导型 LINC00152 受组蛋白乳酰化调节并促进癌细胞侵袭和迁移
DOI：
10.3389/fcimb.2022.913815
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发表时间：
2022
影响因子：
5.7
通讯作者：
中科院分区：
文献类型：
--
作者：
肠道微生物通过表观遗传机制（如长链非编码rna）与宿主基因组相互作用参与发病机制。然而，微生物群诱导长链非编码rna表达改变的机制尚不清楚。在这里，我们量化了人类结肠细胞系在被一种常见的肠道病原体鼠伤寒沙门氏菌SL1344感染后的转录组改变。我们观察到广泛的lncRNAs表达改变。其中，证实LINC00152的表达升高是由肠道细菌源性脂多糖（LPS）诱导的。诱导型LINC00152对沙门氏菌侵袭和炎症反应均有抑制作用。与邻近正常组织相比，临床结直肠癌样本的肿瘤中LINC00152过表达。因此，我们也证明了LINC00152的过表达促进了结直肠癌细胞的迁移和侵袭。一致地，我们观察到肿瘤组织中革兰氏阴性细菌和LPS的丰度增加。综上所述，上述数据提示肿瘤组织中富集的革兰氏阴性菌可能通过调节LINC00152的表达促进肿瘤生长。此外，我们证明LPS通过在LINC00152的启动子上引入组蛋白乳酸化，并降低抑制因子YY1与它的结合效率，从而上调了LINC00152的表达。我们的研究结果为肠杆菌如何影响人类疾病的宿主表观遗传学提供了新的见解。
Gut microbes participate in pathogenesis by interacting with the host genome through epigenetic mechanisms, such as long non-coding RNAs. However, the mechanisms by which the microbiota induce expression alteration of long non-coding RNAs remains unclear. Here, we quantified the transcriptome alteration of human colon cell lines after being infected by a common enteric pathogen Salmonella typhimurium SL1344. We observed a widespread lncRNAs expression alteration. Among them, the elevated expression of LINC00152 was verified and proved to be induced by enteric bacteria-derived lipopolysaccharide (LPS). The inducible LINC00152 were found to inhibit Salmonella invasion and inflammation response. LINC00152 was overexpressed in tumors of the clinical CRC samples compared with adjacent normal tissues. Accordingly, we also demonstrated that overexpression of LINC00152 promoted the migration and invasion of colorectal cancer cells. Consistently, we observed an increased abundance of gram-negative bacteria and LPS in tumors tissue. Taken together, the above data implicated that enriched gram-negative bacteria in tumor tissue might promote tumor growth through modulating the expression of LINC00152. Furthermore, we demonstrated that LPS upregulated the expression of LINC00152 by introducing histone lactylation on its promoter and decreasing the binding efficiency of the repressor, YY1, to it. Our results provide new insights into how enterobacteria affect host epigenetics in human disease.
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影响因子：
24.5
作者：
Flemer B;Lynch DB;Brown JM;Jeffery IB;Ryan FJ;Claesson MJ;O'Riordain M;Shanahan F;O'Toole PW
通讯作者：
O'Toole PW
影响因子：
29.4
作者：
Gradel, Kim O.;Nielsen, Hans L.;Nielsen, Henrik
通讯作者：
Nielsen, Henrik
影响因子：
6.6
作者：
Gao, Yali;Luo, Xiaoling;Zhang, Jun
通讯作者：
Zhang, Jun
DOI：
10.1152/ajpgi.00080.2011
发表时间：
2011-12-01
影响因子：
4.5
作者：
Liu, Xingyin;Wu, Shaoping;Sun, Jun
通讯作者：
Sun, Jun
影响因子：
7
作者：
Castellarin, Mauro;Warren, Rene L.;Holt, Robert A.
通讯作者：
Holt, Robert A.