CircNOL10 Acts as a Sponge of miR-135a/b-5p in Suppressing Colorectal Cancer Progression via Regulating KLF9

摘要

Background: Circular RNAs (circRNAs) have been documented as key regulators during progression of malignant human cancer, including colorectal cancer (CRC). However, the underlying molecular mechanisms of circNOL10 in CRC remain unclear. Methods: The real-time quantitative polymerase chain reaction was used to quantify the expression of circNOL10, miR-135a-5p, miR-135b-5p, and Krüppel-like factor 9 (KLF9). Kaplan–Meier curve was employed to assess the relationship between survival time of CRC patients and expression level of circNOL10. Cell ability of proliferation was measured by Cell Counting Kit8 and colony formation assays. Cell-cycle analysis was performed using flow cytometry assay. In addition, migration and invasion of CRC cell were examined with transwell analysis. The protein expression level was measured with Western blot assay. The interaction relationship of different molecules was analyzed by bioinformatics database and confirmed by dual-luciferase reporter, RNA immunoprecipitation, and RNA pulldown assay. The functional role of circNOL10 in vivo was determined by xenograft experiment. Results: CircNOL10 was decreased in CRC tissues and cells and was associated with poor outcomes. Gain-of-functional experiment revealed that overexpression of circNOL10 constrained proliferation, cell-cycle progression, migration, and invasion of CRC cells, which was abolished by overexpression of miR-135a-5p or miR-135b-5p. Additionally, miR-135a-5p and miR-135b-5p, targets of circNOL10, regulated KLF9 expression in a negative feedback. Consistently, the results of xenograft experiment suggested that overexpression of circNOL10 inhibited tumor growth in vivo. Conclusion: In summary, our results showed that circNOL10 impeded CRC development by mediating proliferation, cell cycle, migration, and invasion by sponging miR-135a-5p and miR-135b-5p, which provided new understanding for CRC treatment.