Hsa_circ_0008434 通过海绵吸附 miR-6838-5p 来调节 USP9X 的表达，从而促进胃癌的生长、迁移和侵袭。
Hsa_circ_0008434 regulates USP9X expression by sponging miR-6838-5p to promote gastric cancer growth, migration and invasion.
机构信息
Department of General Surgery, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, 639 Zhizaoju Road, Shanghai, 200011, China.
Department of Gastroenterology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, 639 Zhizaoju Road, Shanghai, 200011, China.
出版信息
BMC Cancer. 2021 Dec 2;21(1):1289. doi: 10.1186/s12885-021-09052-4.
BACKGROUND
The role of circular RNAs (circRNAs) in the occurrence and development of gastric cancer (GC) has recently attracted increasing interest. The following study investigates the role of a newly discovered hsa_circ_0008434, which has been confirmed to be highly expressed in GC tissues, in regulating GC biological behaviour.
METHODS
High-throughput RNA sequencing was used to identify differentially expressed genes between normal gastric tissues and GC tissues; actinomycin D and RNase R assays were used to determine the stability and loop structure of hsa_circ_0008434; and the miRanda database was used to predict the target genes of hsa_circ_0008434. The role of hsa_circ_0008434 in cell proliferation, migration, and invasion was examined using CCK-8, wound healing, Transwell and colony formation assays. The regulatory relationships among hsa_circ_0008434, microRNA-6838 (miR-6838), and ubiquitin-specific peptidase 9X (USP9X) were determined by dual-luciferase activity assays. The expression of hsa_circ_0008434 and miR-6838 was measured by qPCR; the expression of USP9X was detected by immunohistochemistry and Western blotting. The effects of hsa_circ_0008434 on in vivo tumour growth were assessed in xenograft models.
RESULTS
We found that hsa_circ_0008434 was one of the most upregulated circRNAs in GC tissue versus normal tissue. Further in vitro testing indicated that by acting as a miRNA sponge for miR-6838-5p, hsa_circ_0008434 promotes the expression of USP9X and further increases the proliferation, migration, and invasion of GC cells. In addition, animal studies indicated that hsa_circ_0008434 could promote tumour growth in vivo.
CONCLUSIONS
Hsa_circ_0008434 may promote GC proliferation, invasion and migration by regulating the expression of miR-6838 and USP9X.
背景
环状 RNA（circRNAs）在胃癌（GC）的发生和发展中的作用最近引起了越来越多的关注。本研究旨在探讨一种新发现的 hsa_circ_0008434 在调节 GC 生物学行为中的作用，该 circRNA 已被证实在 GC 组织中高表达。
方法
采用高通量 RNA 测序技术比较正常胃组织和 GC 组织中的差异表达基因；采用放线菌素 D 和 RNase R 实验检测 hsa_circ_0008434 的稳定性和环结构；采用 miRanda 数据库预测 hsa_circ_0008434 的靶基因。采用 CCK-8 法、划痕愈合实验、Transwell 实验和集落形成实验检测 hsa_circ_0008434 对细胞增殖、迁移和侵袭的影响。采用双荧光素酶活性实验确定 hsa_circ_0008434 与 microRNA-6838（miR-6838）和泛素特异性肽酶 9X（USP9X）之间的调控关系。采用 qPCR 检测 hsa_circ_0008434 和 miR-6838 的表达，采用免疫组化和 Western blot 检测 USP9X 的表达。采用异种移植模型检测 hsa_circ_0008434 对体内肿瘤生长的影响。
结果
我们发现 hsa_circ_0008434 是 GC 组织中上调最明显的 circRNA 之一。进一步的体外实验表明，hsa_circ_0008434 通过作为 miR-6838-5p 的 miRNA 海绵，促进 USP9X 的表达，进而增加 GC 细胞的增殖、迁移和侵袭。此外，动物研究表明 hsa_circ_0008434 可促进体内肿瘤生长。
结论
hsa_circ_0008434 可能通过调节 miR-6838 和 USP9X 的表达促进 GC 的增殖、侵袭和迁移。
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