Liver metastasis is the leading cause of death in colorectal carcinoma (CRC). However, little is known about the mechanisms of transferring effector messages between the primary tumor and the site of metastasis. Exosomes provide a novel transfer message method, and exosomal circular RNAs (circRNAs) play critical regulatory roles in cancer biology. In this study, the results showed that the expression of circPABPC1 was aberrantly upregulated in CRC tissues and exosomes. Exosomal circPABPC1 was considered an oncogene by functional experimental analysis in vitro and in vivo. Mechanistically, circPABPC1 recruited KDM4C to the HMGA2 promoter, reduced its H3K9me3 modification and initiated the transcription process in the nucleus. Moreover, cytoplasmic circPABPC1 promoted CRC progression by protecting ADAM19 and BMP4 from miR-874-/miR-1292-mediated degradation. Our findings indicated that exosomal circPABPC1 is an essential regulator in CRC liver metastasis progression by promoting HMGA2 and BMP4/ADAM19 expression. CircPABPC1 is expected to be a novel biomarker and antimetastatic therapeutic target in CRC.
基金：
National Natural Science Foundation of China [81903051]
第一作者机构：[1]Jinzhou Med Univ, Dept Lab Med, Affiliated Hosp, Jinzhou 121001, Peoples R China
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通讯作者：
推荐引用方式(GB/T 7714)：
Li Yang,Hu Jialei,Wang Meng,et al.Exosomal circPABPC1 promotes colorectal cancer liver metastases by regulating HMGA2 in the nucleus and BMP4/ADAM19 in the cytoplasm[J].CELL DEATH DISCOVERY.2022,8(1):doi:10.1038/s41420-022-01124-z.
APA：
Li, Yang,Hu, Jialei,Wang, Meng,Yuan, Yihang,Zhou, Fangyuan...&Liang, Leilei.(2022).Exosomal circPABPC1 promotes colorectal cancer liver metastases by regulating HMGA2 in the nucleus and BMP4/ADAM19 in the cytoplasm.CELL DEATH DISCOVERY,8,(1)
MLA：
Li, Yang,et al."Exosomal circPABPC1 promotes colorectal cancer liver metastases by regulating HMGA2 in the nucleus and BMP4/ADAM19 in the cytoplasm".CELL DEATH DISCOVERY 8..1(2022)
生物学