Downregulation of hsa_circ_0011946 suppresses the migration and invasion of the breast cancer cell line MCF-7 by targeting RFC3

Abstract

IntroductionAlthough some circRNAs have been found to regulate the progression of malignancies, their functions and coupled molecular mechanisms are still unclear. In our study, we sought to assess the underlying molecular mechanisms of circRNAs in breast cancer and therefore explored the differentially expressed circRNAs and co-expression networks, followed by in vitro experiments.Materials and methodsHigh-throughput RNA sequencing was performed to obtain an unbiased profile of circRNA expression. CircRNA-miRNA-mRNA co-expression networks were predicted, and sequence analyses were carried out. The MTT, transwell migration and invasion assay was conducted in Michigan Cancer Foundation-7 cells that had been transfected with si-circRNA and si-negative control (si-NC).ResultsA total of 152 circRNAs were differentially expressed in breast cancer tissues, among which 85 were upregulated and 67 downregulated. Out of these, hsa_circ_0011946 was selected and the subsequent bioinformatics analysis predicted that hsa_circ_0011946 sponging miR-26a/b directly targeted replication factor C subunit 3 (RFC3) and that its knockdown could inhibit RFC3 mRNA and protein expression. Furthermore, hsa_circ_0011946 loss-of-function significantly suppressed the migration and invasion of Michigan Cancer Foundation-7 cells.ConclusionTogether, these results indicate that hsa_circ_0011946 and RFC3 comprise a novel pathway involved in the progression of breast cancer.

Profiles of differentially expressed circRNAs in esophageal and breast cancer

“…21 Studies have shown that abnormal circRNAs are involved in tumorigenesis and disease progression. 22 – 25 However, whether they are general cancer biomarkers or cancer specific biomarkers is not clear. To distinguish the differentially expressed circRNAs between ESCC and BC, we performed a comparative study.…”

Systems biomedicine of primary and metastatic colorectal cancer reveals potential therapeutic targets

“…it is also upregulated in Triple-negative breast cancer (TNBC) [64]. Since expression inhibition of this gene at both mRNA and protein level suppresses the migratory and invasive ability of MCF-7 cell lines [65], this gene would be a therapeutic target for colorectal cancer treatment.…”

Emerging function and potential diagnostic value of circular RNAs in cancer

“…Furthermore, has-circ-0011946 is significantly up-regulated in breast cancer and different breast cancer cell lines. The expression of has-circ-0011946 is positively correlated with RFC3 expression, silencing of has_circ_0011946 inhibits migration and invasion of MCF-7 cell [ 77 ].…”