Chu Yi Min, Peng Hai Xia, Xu Ying, Yang Da Ming, Zhou Feng Li, Li Ji, Kuai Rong, Lin Yong
Department of Gastroenterology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
Department of Endoscopy, Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
J Dig Dis. 2017 Mar;18(3):169-178. doi: 10.1111/1751-2980.12463.
MicroRNA-1254 (miR-1254) has not been studied in colorectal cancer (CRC) to date. This study aimed to investigate the inhibitory mechanism of miR-1254 in CRC tumorigenesis.
MiR-1254 expression was examined using real-time polymerase chain reaction in CRC and adjacent non-tumorous tissues. The correlation between miR-1254 expressions and proliferation and migration of cancer cells was determined using the CCK-8 and transwell assays. RNA sequencing was used to identify differentially expressed genes downstream from miR-1254. A luciferase reporter assay was used to confirm the direct interaction between miR-1254 and its predicted target gene, PSMD10. Moreover, PSMD10 was either overexpressed or silenced in colon carcinoma cells overexpressing miR-1254 to determine whether their interaction contributed to CRC migration and epithelial-mesenchymal transition (EMT).
Significantly lower miR-1254 expressions were observed in CRC tissues than in adjacent non-tumorous tissues. Exogenous miR-1254 expression suppressed the migration of colon carcinoma cell lines SW1116 and HCT116. RNA sequencing and luciferase assays revealed that miR-1254 directly binded to the 3'-untranslated region of PSMD10, an important regulator of EMT and cell migration. PSMD10 knockdown inhibited EMT and colon cancer cell migration, whereas PSMD10 overexpression reversed the inhibition of EMT and cell migration caused by miR-1254.
MiR-1254 may act as a tumor suppressor in CRC and may inhibit CRC migration by directly targeting PSMD10 to suppress the EMT process.
迄今为止，尚未对微小RNA-1254（miR-1254）在结直肠癌（CRC）中的作用进行研究。本研究旨在探讨miR-1254在CRC肿瘤发生中的抑制机制。
采用实时聚合酶链反应检测CRC组织及癌旁非肿瘤组织中miR-1254的表达。采用CCK-8和transwell实验检测miR-1254表达与癌细胞增殖和迁移的相关性。通过RNA测序鉴定miR-1254下游差异表达基因。采用荧光素酶报告基因实验证实miR-1254与其预测靶基因PSMD10之间的直接相互作用。此外，在过表达miR-1254的结肠癌细胞中过表达或沉默PSMD10，以确定它们之间的相互作用是否促进CRC迁移和上皮-间质转化（EMT）。
与癌旁非肿瘤组织相比，CRC组织中miR-1254表达显著降低。外源性miR-1254表达抑制结肠癌细胞系SW1116和HCT116的迁移。RNA测序和荧光素酶实验表明，miR-1254直接与PSMD10的3'-非翻译区结合，PSMD10是EMT和细胞迁移的重要调节因子。敲低PSMD10可抑制EMT和结肠癌细胞迁移，而过表达PSMD10可逆转miR-1254对EMT和细胞迁移的抑制作用。
miR-1254可能作为CRC的肿瘤抑制因子，通过直接靶向PSMD10抑制EMT过程，从而抑制CRC迁移。
