Gut butyrate-producing organisms correlate to Placenta Specific 8 protein: Importance to colorectal cancer progression
Gut butyrate-producing organisms correlate to Placenta Specific 8 protein: Importance to colorectal cancer progression
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DOI：
10.1016/j.jare.2019.11.005
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发表时间：
2020-03-01
影响因子：
10.7
通讯作者：
Huang, Chi-Jung
中科院分区：
文献类型：
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作者：
Huang, Chi-Cheng;Shen, Ming-Hung;Huang, Chi-Jung
结直肠癌（CRC）根治性切除术后，肿瘤经常发生转移或复发。胎盘特异性8 （PLAC8）在粪便中表达增加，可能与结直肠癌复发有关。了解PLAC8在CRC复发中的作用及其临床意义可能有助于制定预防CRC复发和恶化的策略。通过临床组织、细胞和动物模型来阐明PLAC8在结直肠癌肿瘤发生、侵袭和迁移中的作用。下一代16S核糖体DNA测序已被用于评估结直肠癌患者粪便中的肠道微生物群。我们发现PLAC8在晚期结直肠癌患者的组织中表达上调。在我们的体外研究中，PLAC8在有丝分裂细胞中受到动态调节。有丝分裂时，过表达的PLAC8在中心体上成核，因此，过表达的PLAC8可能促进细胞的生长和迁移（均p < 0.05）。在异种移植小鼠模型中也证实了PLAC8对CRC细胞的致瘤性和侵袭性作用。我们进一步发现，在结直肠癌患者的粪便中，两种产生丁酸盐的生物，丁酸球菌和普雷沃氏菌的水平降低。我们发现，丁酸盐可下调PLAC8的表达并诱导过表达PLAC8的细胞凋亡。我们的数据表明，PLAC8基因和蛋白的表达以及肠道菌群，特别是产生丁酸盐的微生物的生态失调，可能是结直肠癌进展的指标。(C) 2019作者。由Elsevier B.V.代表开罗大学出版。
Tumor metastasis or recurrence often occurs in patients with curative resection of colorectal cancer (CRC). Placental-specific 8 (PLAC8), which has increased expression in stool, may be associated with CRC recurrence. Insights into the role of PLAC8 in CRC recurrence and its clinical significance may support to develop strategies for preventing CRC recurrence and deterioration. Clinical tissues, cell and animal models were used to clarify the roles of PLAC8 in CRC tumorigenesis, invasion, and migration. Next-generation sequencing of 16S ribosomal DNA has been used to assess the gut microbiota in stool of CRC patients. We found that PLAC8 was upregulated in tissues from patients with late-stage CRC. In our in vitro studies, PLAC8 was dynamically regulated in mitotic cells. Overexpressed PLAC8 was nucleated at the centrosome during mitosis, and therefore, PLAC8 overexpression might increase cell growth and migration (all p < 0.05). The tumorigenic and invasive effects of PLAC8 on CRC cells were also confirmed in a xenograft mouse model. We further identified reduced levels of two butyrate-producing organisms, Butyricicoccus and Prevotella spp., in stools from CRC patients. We found that butyrate down-regulated PLAC8 expression and induced apoptosis in PLAC8-overexpressing cells. Our data suggests that PLAC8 gene and protein expression and dysbiosis of gut microflora, especially in butyrate-producing microorganisms, may be indicators of CRC progression. (C) 2019 The Authors. Published by Elsevier B.V. on behalf of Cairo University.