Abstract

BackgroundA 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.MethodsWe 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.ResultsThe 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.ConclusionOur 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.

Highlights

  • A growing body of evidence indicates that abnormal expression of circular RNAs plays a crucial role by acting as molecular sponges of microRNAs in various diseases, including cancer

  • We detected the expression of circCCDC85A in 58 breast cancer tissues and 40 normal breast tissues; the fluorescence in situ hybridization (FISH) analysis revealed that the expression of circCCDC85A was significantly lower in breast cancer tissues than that in normal breast tissues (Fig. 1F)

  • CircCCDC85A may serve as a molecular sponge of miR-550a-5p and restore miR550a-5p-mediated targeting repression of tumor suppressor gene MOB1A in breast cancer (Fig. 7)

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Summary

Introduction

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. We explored whether circCCDC85A could function as a miR-550a-5p sponge and influence breast cancer progression. Increasing studies report that several types of molecules, such as non-coding RNAs (ncRNAs), play a crucial role in these processes [6]. It has been found that circRNAs are involved in the progression of various tumors by serving as microRNA (miRNA) sponges, translating polypeptides or proteins, interacting with proteins, and regulating gene transcription and splicing processes [11,12,13,14,15]. Several studies have shown that some exon-derived circRNAs, such as ciRS-7, circ-Sry, circ-ITCH, and circHIPK3, are rich in miRNA response elements (MRE) and could act as miRNA sponges through competitive endogenous RNA (ceRNA) mechanisms to competitively bind miRNAs, thereby further resulting in the negative regulation of miRNAs and their downstream target genes [9, 11, 16,17,18,19,20]

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