Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin, China.
Department of Geriatric, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, Beijing, China.
Cell Transplant. 2021 Jan-Dec;30:9636897211007055. doi: 10.1177/09636897211007055.
Circular RNAs (circRNAs) have been proved to act crucial roles in multiple malignancies including gastric cancer (GC). Retinoic acid induced 14 (RAI14) acts as an oncogene in human cancers, but the underlying mechanisms by which RAI14 is regulated by circRNA/miRNA axis remain elusive. The clinical value of RAI14, miR-23b-3p and circNFATC3 was estimated by The Cancer Genome Atlas and fluorescence in situ hybridization. The interplay between miR-23b-3p and RAI14 or circNFATC3 was determined by qRT-PCR, Western blot, luciferase gene report and RIP assays. Biological function assays and a subcutaneous xenograft model were executed to unveil the role of circNFATC3/miR-23b-3p/RAI14 axis in GC cells. As a consequence, upregulation of RAI14 and circNFATC3 or downregulation of miR-23b-3p was associated with poor prognosis in patients with GC. Restored miR-23b-3p depressed cell proliferation, colony formation, and cell invasion by targeting RAI14, whereas RAI14 facilitated cell progression and reversed the anti-tumor effects of miR-23b-3p in GC cells. Then, circNFATC3 had a co-localization with miR-23b-3p in the cytoplasm in GC tissue cells and could act as a sponge of miR-23b-3p in GC cell line. Silencing of circNFATC3 inhibited cell growth and in vivo tumorigenesis by upregulating miR-23b-3p and downregulating RAI14. In conclusion, our findings indicated that RAI14 facilitated cell growth and invasion and was regulated by circNFATC3/miR-23b-3p axis in GC.
环状 RNA（circRNAs）已被证明在多种恶性肿瘤中发挥重要作用，包括胃癌（GC）。维甲酸诱导 14（RAI14）在人类癌症中作为癌基因发挥作用，但 RAI14 如何受 circRNA/miRNA 轴调控的机制仍不清楚。通过癌症基因组图谱和荧光原位杂交来评估 RAI14、miR-23b-3p 和 circNFATC3 的临床价值。通过 qRT-PCR、Western blot、荧光素酶基因报告和 RIP 测定来确定 miR-23b-3p 与 RAI14 或 circNFATC3 之间的相互作用。进行了生物学功能测定和皮下异种移植模型，以揭示 circNFATC3/miR-23b-3p/RAI14 轴在 GC 细胞中的作用。结果表明，RAI14 和 circNFATC3 的上调或 miR-23b-3p 的下调与 GC 患者的预后不良相关。恢复 miR-23b-3p 通过靶向 RAI14 抑制细胞增殖、集落形成和细胞侵袭，而 RAI14 促进 GC 细胞的进展并逆转 miR-23b-3p 的抗肿瘤作用。然后，circNFATC3 在 GC 组织细胞的细胞质中与 miR-23b-3p 存在共定位，并且可以在 GC 细胞系中作为 miR-23b-3p 的海绵。沉默 circNFATC3 通过上调 miR-23b-3p 和下调 RAI14 抑制细胞生长和体内肿瘤发生。总之，我们的研究结果表明，RAI14 通过 circNFATC3/miR-23b-3p 轴促进 GC 细胞的生长和侵袭。
