CircNRIP1 promotes proliferation, migration and phenotypic switch of Ang II-induced HA-VSMCs by increasing CXCL5 mRNA stability via recruiting IGF2BP1.

Circular RNA (circRNA) has been found to be differentially expressed and involved in regulating the processes of human diseases, including thoracic aortic dissection (TAD). However, the role and mechanism of circNRIP1 in the TAD process are still unclear. GEO database was used to screen the differentially expressed circRNA and mRNA in type A TAD patients and age-matched normal donors. Angiotensin II (Ang II)-induced human aortic vascular smooth muscle cells (HA-VSMCs) were used to construct TAD cell models. The expression levels of circNRIP1, NRIP1, CXC-motif chemokine 5 (CXCL5) and IGF2BP1 were detected by quantitative real-time PCR. Cell proliferation and migration were determined by EdU assay, transwell assay and wound healing assay. The protein levels of synthetic phenotype markers, contractile phenotype markers, CXCL5 and IGF2BP1 were tested by western blot analysis. The interaction between IGF2BP1 and circNRIP1/CXCL5 was confirmed by RIP assay, and CXCL5 mRNA stability was assessed by actinomycin D assay. CircNRIP1 was upregulated in TAD patients and Ang II-induced HA-VSMCs. Knockdown of circNRIP1 suppressed Ang II-induced proliferation, migration and phenotypic switch of HA-VSMCs. Also, high expression of CXCL5 was observed in TAD patients, and its knockdown could inhibit Ang II-induced HA-VSMCs proliferation, migration and phenotypic switch. Moreover, CXCL5 overexpression reversed the regulation of circNRIP1 knockdown on Ang II-induced HA-VSMCs functions. Mechanistically, circNRIP1 could competitively bind to IGF2BP1 and subsequently enhance CXCL5 mRNA stability. CircNRIP1 might contribute to TAD progression by promoting CXCL5 mRNA stability via recruiting IGF2BP1.

Circ-ATIC regulates esophageal squamous cell carcinoma growth and metastasis through miR-1294/PBX3 pathway.

Esophageal squamous cell carcinoma (ESCC) is a digestive tract malignancy associated with poor clinical outcome. Growing evidence have elucidated that circular RNAs (circRNAs) play important roles in the pathological process of ESCC. However, the detailed mechanisms how circRNAs modulate the development of ESCC remain largely unknown. Our study aimed to decipher the role and mechanism of circ-ATIC (also termed as circRNA_0058063) in regulating the progression of ESCC. We found that circ-ATIC and its host gene ATIC were significantly increased in ESCC tissues and cells compared with the adjacent noncancerous tissues or normal esophagus epithelial cell. Circ-ATIC knockdown substantially reduced proliferation and the number of invaded ESCC cells and retarded EMT process, reflecting by the decreased N-cadherin and elevated E-cadherin. However, the level of host gene ATIC was not changed under circ-ATIC suppression. It was predicted that circ-ATIC could bind to miR-1294 and serve as a sponge RNA. The luciferase reporter assay and RNA immunoprecipitation (RIP) assay confirmed their relations. MiR-1294 was decreased in ESCC tissues and cells, which was reversely correlated with circ-ATIC level. Furthermore, PBX3 was predicted and proved to be a downstream direct target of miR-1294. PBX3 mRNA and protein were obviously upregulated in ESCC tumor tissues and cells. PBX3 overexpression could reverse the suppressive roles of miR-1294 mimics on ESCC proliferation and invasion. In an xenograft nude mice model, stable transfection of sh-circ-ATIC significantly retarded the growth of tumor and suppressed VEGF and Ki67. Collectively, circ-ATIC promoted ESCC proliferation and invasion by regulating miR-1294/PBX3 axis.