Circular RNA circCCDC85A inhibits breast cancer progression via acting as a miR-550a-5p sponge to enhance MOB1A expression

Abstract

Background A growing body of evidence indicates that abnormal expression of circular RNAs (circRNAs) plays a crucial role by acting as molecular sponges of microRNAs (miRNAs) in various diseases, including cancer. In this study, we explored whether circCCDC85A could function as a miR-550a-5p sponge and influence breast cancer progression. Methods We detected the expression of circCCDC85A in breast cancer tissues and cells using fluorescence in situ hybridization (FISH) and quantitative reverse transcription polymerase chain reaction (qRT-PCR). CCK-8 and colony formation assay were used to detect the proliferative ability of breast cancer cells. Wound healing assay and transwell migration and invasion assays were used to detect the migrative and invasive abilities of breast cancer cells. We also examined the interactions between circCCDC85A and miR-550a-5p using FISH, RNA-binding protein immunoprecipitation (RIP), and luciferase reporter assay. Moreover, we performed luciferase reporter assay, qRT-PCR, and Western blot to confirm the direct targeting of miR-550a-5p to MOB1A. Results The expression of circCCDC85A in breast cancer tissues was obviously lower than that in normal breast tissues. Over-expression of circCCDC85A substantially inhibited the proliferative, migrative, and invasive ability of breast cancer cells, while knocking down of circCCDC85A enhanced the aforementioned properties of breast cancer cells. Moreover, enforced expression of circCCDC85A inhibits the oncogenic activity of miR-550a-5p and increases the expression of MOB1A targeted by miR-550a-5p. Further molecular mechanism research showed that circCCDC85A may act as a molecular sponge for miR-550a-5p, thus restoring miR-550a-5p-mediated targeting repression of tumor suppressor MOB1A in breast cancer cells. Conclusion Our findings provide novel evidence that circCCDC85A inhibits the progression of breast cancer by functioning as a molecular sponge of miR-550a-5p to enhance MOB1A expression.

miR-550a-5p promotes the proliferation and migration of hepatocellular carcinoma by targeting GNE via the Wnt/β-catenin signaling pathway

“…identified miR-550a-5p as a tumor promoter by targeting LIMD1 in lung adenocarcinoma [25]. In a recent study, as a downstream target molecule of circCCDC85A, miR-550a-5p promoted breast cancer progression by regulating MOB1A [26]. Circular RNA circCCDC85A inhibits breast cancer progression by acting as a miR-550a-5p sponge to enhance MOB1A expression.…”

Emerging concepts of miRNA therapeutics: from cells to clinic

“…Additional studies highlight the potential of naturally occurring transcripts as a source for therapeutically usable miRNA sponges. Recently, the circular RNA hsa_circ_0120472, which includes two predicted miRNA binding sites, has been shown to act as an efficient sponge to inhibit miR-550a in human breast cancer cells [27]. The yet increasing number of new strategies that are currently being pursued to modify and reverse pathological miRNA expression changes will certainly promote the development of therapeutic approaches.…”

Circular RNAs in EMT-driven metastasis regulation: modulation of cancer cell plasticity, tumorigenesis and therapy resistance

“…The action of circRNAs in affecting tumor progression is mainly performed via sponging miRNAs. For example, circCCDC85A sponges miR-550a-5p, increasing MOB1A levels and impairing breast tumor progression [ 38 ]. Tumor progression and proliferation are tightly regulated by the function of circRNAs [ 39 ].…”