CircRNA CDR1as knockdown inhibits progression of non‐small‐cell lung cancer by regulating miR‐219a‐5p/SOX5 axis

Abstract

Background Circular RNAs (circRNAs) participate in the development of human cancers by regulating multiple cell processes. CircRNA antisense to the cerebellar degeneration‐related protein 1 transcript (circCDR1as) expression is dysregulated in many cancers, including non‐small‐cell lung cancer (NSCLC). However, the mechanism by which circCDR1as mediates the development of NSCLC remains unknown. Methods A total of 30 paired cancer and normal tissues were collected from patients with NSCLC. The expression levels of circCDR1as, microRNA (miR)‐219a‐5p and Sex determining region Y‐box protein 5 (SOX5) were measured in tissues or cells by quantitative real‐time polymerase chain reaction or western blot. Cell viability, apoptosis, migration and invasion were detected by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐tetrazolium bromide, colony formation, flow cytometry and transwell assays, respectively. The target relationship between miR‐219a‐5p and circCDR1as or SOX5 was validated by dual‐luciferase reporter assay. Results CircCDR1as expression was elevated in NSCLC tissues and cells in comparison to the matched controls. Interference of circCDR1as led to obvious inhibition of cell viability, migration and invasion and increase of apoptosis in NSCLC cells. MiR‐219a‐5p acted as a target of circCDR1as and miR‐219a‐5p downregulation attenuated the regulatory effect of circCDR1as silencing on NSCLC progression. Moreover, miR‐219a‐5p targeted SOX5 to repress the progression of NSCLC in vitro. Besides, circCDR1as knockdown reduced the expression of SOX5 by increasing miR‐219a‐5p level. Conclusion Knockdown of circCDR1as inhibited the progression of NSCLC by decreasing cell viability, migration and invasion and increasing apoptosis by upregulating miR‐219a‐5p and downregulating SOX5.

CircKIAA0907 Retards Cell Growth, Cell Cycle, and Autophagy of Gastric Cancer In Vitro and Inhibits Tumorigenesis In Vivo via the miR-452-5p/KAT6B Axis

“…Circular ribonucleic acids (circRNAs) are covalently closed-loop structures and function as crucial regulatory molecules in cancer oncogenesis [ 4 , 5 ]. Li et al proved that circRNA CDR1as was an oncogenic factor in nonsmall-cell lung cancer [ 6 ], and Lin and Cai claimed that circ-EGLN3 enhanced the proliferation and aggressiveness of renal cell carcinoma cells [ 7 ]. Circ_LARP4 was shown to inhibit ovarian cancer cell proliferation and migration [ 8 ], and the anticancer role of circMTO1 was demonstrated in rectal cancer [ 9 ].…”

<p>CircRNA CDR1as/miR-1287/Raf1 Axis Modulates Hepatocellular Carcinoma Progression Through MEK/ERK Pathway</p>

“…Besides, we determine that circ_CDR1as is a stable circRNA, suggesting that circ_CDR1as might be a diagnostic biomarker for HCC patients. Besides, circ_CDR1as could also promote the development of nonsmall-cell lung cancer (NSCLC), 27 nasopharyngeal carcinoma, 28 while inhibit ovarian cancer progression, 29 suggesting its oncogenic role. The altered expression of circ_CDR1as in HCC prompts us to investigate the function of circ_CDR1as in vitro and in vivo.…”

“…As reported, miR-1287 embraces important diagnostic and prognostic value in colorectal cancer. 27 In breast cancer, miR-1287 could be sponged by circ-UBE2D2 to affect tumor progression. 28 And, in NSCLC, miR-1287 functions as the target of circ_0026134 to regulate cell proliferation and invasion of A549 and H1299 cells.…”

The expanding role of CDR1‐AS in the regulation and development of cancer and human diseases

“…inhibits progression, migration, and invasion by decreasing the level of SOX5 is revealed in the 2020 study by Y. Li et al (2020).…”

“…Overexpression of miR‐219a‐5p as a result of silencing of ciR‐7 inhibits progression, migration, and invasion by decreasing the level of SOX5 is revealed in the 2020 study by Y. Li et al (2020).…”