Gut Microbiota Dysbiosis Accelerates Prostate Cancer Progression Through Increased LPCAT1 Expression and Enhanced DNA Repair Pathways.
Gut Microbiota Dysbiosis Accelerates Prostate Cancer Progression Through Increased LPCAT1 Expression and Enhanced DNA Repair Pathways.
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肠道菌群失调通过增加 LPCAT1 表达和增强 DNA 修复途径加速前列腺癌进展
DOI：
10.3389/fonc.2021.679712
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发表时间：
2021
影响因子：
4.7
通讯作者：
Jiang H
中科院分区：
文献类型：
--
作者：
Liu Y;Yang C;Zhang Z;Jiang H
肠道微生物群失调与癌症的发展和进展有关。我们以前的研究表明，Ruminococcus在CRPC（去势抵抗性前列腺癌）中比HSPC（激素敏感性前列腺癌）个体更丰富。在这里，我们确定了前列腺癌（PCa）进展中微生物群失调的潜在机制。宏基因组学用于验证CRPC和HSPC个体之间的肠道微生物差异。通过将CRPC或HSPC个体的粪便悬浮液转移至TRAMP小鼠来进行粪便微生物群移植（FMT）。然后，测定小鼠的前列腺组织病理学和肠道微生物群组成。由于瘤胃球菌被证明与磷脂代谢相关，我们使用脂质组学来检查小鼠的粪便脂质谱。同时检测小鼠前列腺中磷脂重塑的关键酶LPCAT 1的表达。同时，通过微生物功能预测和LPCAT 1基因组富集分析（Gene Set Enrichment Analysis，LPCAT 1 GSEA），进一步检测了小鼠前列腺中RAD 51和DNA-PKcs的表达。结果表明，肠道瘤胃球菌在CRPC个体中显著更丰富。使用CRPC粪便的FMT加速小鼠的PCa进展并增加其肠道瘤胃球菌丰度。在CRPC FMT处理的小鼠中，包括溶血磷脂酰胆碱和磷脂酰胆碱在内的大部分粪便脂质上调，伴随着小鼠前列腺中LPCAT 1、RAD 51和DNA-PKcs的表达增强。我们报道了CRPC个体和接受其粪便悬浮液的小鼠的肠道中大量的瘤胃球菌定植，并揭示了瘤胃球菌通过上调LPCAT 1和DNA修复蛋白表达在PCa进展中的促进能力。该细菌及其下游通路可能成为未来PCa治疗的靶点。
Gut microbiota dysbiosis is related to cancer development and progression. Our previous study showed that Ruminococcus was more abundant in CRPC (Castration-resistant prostate cancer) than HSPC (Hormone-sensitive prostate cancer) individuals. Here, we determined the potential mechanism of microbiota dysbiosis in prostate cancer (PCa) progression. Metagenomics was used to verify the gut microbial discrepancies between CRPC and HSPC individuals. Fecal microbiota transplantation (FMT) was performed by transferring the fecal suspension of CRPC or HSPC individuals to TRAMP mice. Afterwards, the mice’s prostate histopathology and gut microbiota composition were determined. Since Ruminococcus was demonstrated to correlate with phospholipid metabolism, we used lipidomics to examine the mice’s fecal lipid profiles. The expression of LPCAT1 the key enzyme for phospholipid remodeling in mice prostate was also examined. Meanwhile, both microbial functions prediction and LPCAT1 GSEA analysis (Gene Set Enrichment Analysis) indicated DNA repair pathways, we further determined the expressions of RAD51 and DNA-PKcs in mice prostate. The results showed that gut Ruminococcus was significantly more abundant in CRPC individuals. FMT using CRPC feces accelerated mice’s PCa progression and increased their gut Ruminococcus abundance. Majority of fecal lipids including lysophosphatidylcholine and phosphatidylcholine were upregulated in CRPC FMT treated mice, accompanied with enhanced expressions of LPCAT1, RAD51, and DNA-PKcs in mice prostate. We reported an abundant colonization of Ruminococcus in the gut of CRPC individuals and mice receiving their fecal suspensions, and revealed the promotive capability of Ruminococcus in PCa progression via upregulating LPCAT1 and DNA repair protein expressions. The bacterium and its downstream pathways may become the targets of therapies for PCa in the future.
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影响因子：
0.9
作者：
Hsu FM;Zhang S;Chen BP
通讯作者：
Chen BP
影响因子：
4.7
作者：
Mansilla, Francisco;da Costa, Kerry-Ann;Wang, Shuli;Kruhoffer, Mogens;Lewin, Tal M.;Orntoft, Torben F.;Coleman, Rosalind A.;Birkenkamp-Demtroder, Karin
通讯作者：
Birkenkamp-Demtroder, Karin
影响因子：
5.2
作者：
Doherty, Rachel E.;Bryant, Helen E.;Sisley, Karen
通讯作者：
Sisley, Karen
影响因子：
7
作者：
Park, Tansol;Ma, Lu;Yu, Zhongtang
通讯作者：
Yu, Zhongtang
DOI：
10.1186/s13046-017-0525-1
发表时间：
2017-05-12
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Du Y;Wang Q;Zhang X;Wang X;Qin C;Sheng Z;Yin H;Jiang C;Li J;Xu T
通讯作者：
Xu T