CircRUNX1 functions as an oncogene in colorectal cancer by regulating circRUNX1/miR‐485‐5p/SLC38A1 axis

Abstract

Background Circular RNAs (circRNAs) have emerged as vital regulators in human cancers, including colorectal cancer (CRC). In this study, we aimed to explore the roles of circRUNX1 in CRC. Methods The levels of circRUNX1, RUNX1 mRNA, solute carrier family 38 member 1 (SLC38A1) mRNA and microRNA‐485‐5p (miR‐485‐5p) were determined by quantitative real‐time polymerase chain reaction (qRT‐PCR) analysis. The protein level of SLC38A1 was measured by Western blot assay. Cell colony formation, migration, invasion and apoptosis were assessed by colony formation assay, wound‐healing assay, Transwell assay and flow cytometry analysis, respectively. The interaction between miR‐485‐5p and circRUNX1 or SLC38A1 was verified by dual‐luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The levels of extracellular glutamine, intracellular glutamate and α‐ketoglutarate (α‐KG) were measured with specific kits. The functional role of circRUNX1 in CRC development in vivo was explored by murine xenograft model assay. Results CircRUNX1 was upregulated in CRC tissues and cells compared with normal tissues and cells. CircRUNX1 deficiency restrained CRC cell colony formation, migration, invasion and glutaminolysis and induced apoptosis in vitro as well as blocked tumour growth in vivo. CircRUNX1 directly sponged miR‐485‐5p, which negatively modulated SLC38A1 expression in CRC cells. The effects of circRUNX1 knockdown on CRC cell colony formation, migration, invasion, apoptosis and glutaminolysis were reversed by miR‐485‐5p inhibition. Moreover, miR‐485‐5p overexpression repressed the malignant behaviours of CRC cells, with SLC38A1 elevation overturned the impacts. Conclusion CircRUNX1 promoted CRC cell growth, metastasis and glutamine metabolism and repressed apoptosis by elevating SLC38A1 through sponging miR‐485‐5p, which might provide a novel target for CRC treatment.

Hsa_circ_0003602 Contributes to the Progression of Colorectal Cancer by Mediating the miR-149-5p/SLC38A1 Axis

“…SLC38A1 has been testified to have elevated expression and play an important part in multifarious malignancies. 30,31 Also, Yu et al 32 claimed that circRUNX1 deficiency suppressed the growth, motility, and glutaminolysis and induced apoptosis through the miR-485-5p/SLC38A1 axis. Here, we discovered that SL-C38A1 was raised in CRC.…”

Up-regulated Circular RNAs in Colorectal Cancer: New Entities for Therapy and Tools for Identification of Therapeutic Targets

“…Circ RUNX1 (Figure 2) was up-regulated in CRC tissues and cells in comparison to normal colonic tissues and cells (70). Its knockdown restrained CRC colony formation, migration, invasion, glutaminolysis, induced apoptosis in vitro and blocked tumor growth in immuno-deficient mice (70). Circ RUNX1 sponged miR-485-5p leading to up-regulation of SLC38A1.…”

Roles of circular RNAs in colorectal cancer (Review)

“…During serum deprivation, circ-ACC1, which derives from preACC1 mRNA, increases glycolysis and fatty acid oxidation to adapt the metabolic change of HCT116 cells ( 77 ). Another novel circRNA, circRUNX1, has been found to promote glutamine metabolism and to repress apoptosis by upregulating solute carrier family 38 member 1 SLC38A1 through miR-485-5p ( 78 ).…”

“…Additionally, as a clearer picture of the complex network of non-coding RNA regulation is built, the clinical value of circRNAs has become more evident. The roles of other circRNAs in biological processes in CRC are listed in Table II ( 38 , 45 , 55 – 60 , 62 – 65 , 69 , 72 – 76 , 78 – 82 , 87 – 126 ).…”