Circular RNA hsa_circ_0043278 inhibits breast cancer progression via the miR-455-3p/EI24 signalling pathway

Abstract

Background Breast cancer (BC) is one of the major malignancies worldwide. Circular ribonucleic acids (circRNAs) are a class of conserved ribonucleic acid (RNA) molecules that play important roles in various diseases. Recently, circRNAs have been suggested to have diagnostic value and may function as potential diagnostic biomarkers for BC. Previously, hsa_circ_0043278 was found to be downregulated in human BC. However, its role in human BC has not yet been identified. Methods The levels of hsa_circ_0043278 in BC cell lines were verified by quantitative reverse transcription–polymerase chain reaction (qRT–PCR). The overexpression vector and short hairpin RNA (shRNA) of hsa_circ_0043278 were transfected into MDA-MB-231 and MCF-7 cells, respectively. The effects of hsa_circ_0043278 on tumour cell growth, migration and invasion were measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT), colony formation, wound healing and Transwell assays in vitro. A xenograft experiment was conducted to validate the inhibitory effect of hsa_circ_0043278 on tumour growth. The interaction between hsa_circ_0043278 and miR-455-3p was confirmed by a dual-luciferase reporter assay. Mimics and inhibitors of miR-455-3p were designed to confirm the influence of hsa_circ_0043278 on the hsa_circ_0043278/miR-455-3p/etoposide-induced gene 24 (EI24) axis. Results Hsa_circ_0043278 was downregulated in BC cell lines. Furthermore, overexpression of hsa_circ_0043278 notably decreased BC cell viability and inhibited BC cell migration and invasion in vitro and suppressed tumour growth in vivo. Downregulation of hsa_circ_0043278 led to the opposite results. Hsa_circ_0043278 expression was negatively correlated with that of miR-455-3p. In addition, mechanistic investigation proved that hsa_circ_0043278 directly bound to miR-455-3p and regulated EI24 and NF-κB expression in BC cells. Conclusion Hsa_circ_0043278 acts as a tumour suppressor gene in BC through the hsa_circ_0043278/miR-455-3p/EI24 axis and may be regarded as a new prognostic predictor or potential therapeutic target in BC.

Hsa_circ_0000106 Acts as a Tumor Promoter in Pancreatic Cancer by Targeting the MiR-455–3p/HDAC4

“…Furthermore, there has evidence that many circRNAs act as miR-455–3p sponges across cancer progression. For example, circ_0043278 sponges miR-455–3p to inhibit breast cancer 22 , circ_SEC24A sponging miR-455–3p and accelerates tumor progression 23 , and circ_CSNK1G1 acts as a molecular sponge for miR-455–3p to promote the progression of colorectal cancer 24 . Previous studies have confirmed that multiple circRNAs act as molecular sponges of miR-455–3p to regulate cancer progression.…”

“…Additionally, circRNAs that act as miR-455-3p sponges and affect cancer progression have been identified. circ_0043278 can sponge miR-455-3p to regulate etoposide-induced gene 24 expression, thereby inhibiting breast cancer [22]. Circ _SEC24A accelerates tumor progression in hepatocellular carcinoma by sponging miR-455-3p to increase PPM1F expression [23].…”

Modulation of cancer progression by circRNA/ NF-kB axis

“…Mechanistically, this circRNA by interaction with DEAH (Asp-Glu-Ala-His) box helicase 15 (DHX15) blocked DHX15-NF-κB p65 positive feedback loop, thereby suppressing breast cancer progression (69). Similar to circRNF10, hsa_circ_0043278 functions as a tumor suppressor gene, inhibits breast cancer progression by sponging miR-455-3p, increasing the level of EI24, reducing the activity of NF-κB pathway (70). Considering the role of RBPs in the biosynthesis of circRNA, a recent study indicated that tumor exosomal SERPINE2-derived hsa_circ_0001103 (cSERPINE2) was shuttled to tumor associated macrophages and remarkably increased MALT1, a vital regulator of immune responses, elevated the levels of IL-6 via stimulating NF-κB signaling, leading to promoting proliferation and invasion of breast cancer cells (71) (Figure 2).…”