Super-enhancer-associated long noncoding RNA RP11-569A11.1 inhibited cell progression and metastasis by regulating IFIT2 in colorectal cancer.

Abstract

BackgroundRecent studies have revealed that super‐enhancer–associated long noncoding RNAs (SE‐LncRNAs) act pivotal roles in carcinogenesis. This study aimed to report the identification of a novel SE‐LncRNA, RP11‐569A11.1, and its functional role in colorectal cancer (CRC) progression.MethodsArraystar human SE‐LncRNA microarray was performed to detect differentially expressed SE‐LncRNAs in CRC tissues. RT‐qPCR was conducted to detect the expression level of RP11‐569A11.1 in CRC tissues and cells. The ROC curve was used to analyze the sensitivity and specificity of RP11‐569A11.1 in CRC diagnosis. CCK‐8 assay, colony formation assay, flow cytometry assay, and transwell assay were used to study the function of RP11‐569A11.1. RNA‐seq array was performed to analyze the potential downstream target gene of RP11‐569A11.1. Western blot assay was conducted to measure the protein level of interferon‐induced protein with tetratricopeptide repeat 2 (IFIT2).ResultsA total of 23 (15 up‐ and 8 downregulated) significantly expressed SE‐LncRNAs were identified in CRC tissues. The top 8 upregulated SE‐LncRNAs were RP11‐893F2.9, PTCSC1, RP11‐803D5.4, AC005592.2, LINC00152, LINC01232, AC017002.1, and RP4‐673M15.1, and the top 8 downregulated SE‐LncRNAs were RP11‐569A11.1, RP11‐245G13.2, RP11‐556N21.1, U91328.19, AX748340, CTD‐2337J16.1, CATG00000108830.1, and RP11‐670E13.2. Of which, RP11‐569A11.1 was found to be significantly downregulated in CRC tissues and cells. ROC curve analysis showed the area under the curve (AUC) of 0.77 [95% confidence interval (CI), 0.660–0.884, p < 0.001], and the diagnostic sensitivity and specificity were 74.29% and 71.43%, respectively. Functionally, overexpression of RP11‐569A11.1 inhibited CRC cell proliferation, migration and invasion, and induced cell apoptosis, while knockdown of RP11‐569A11.1 generated an opposite effect. Mechanistically, RP11‐569A11.1 positively regulated IFIT2 expression in CRC cells.ConclusionRP11‐569A11.1 inhibited CRC tumorigenesis by IFIT2‐dependent and could serve as a promising diagnostic biomarker in CRC.