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

Background: Recent 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.

Methods: Arraystar 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).

Results: A 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.

Conclusion: RP11-569A11.1 inhibited CRC tumorigenesis by IFIT2-dependent and could serve as a promising diagnostic biomarker in CRC.