Increased Expression of Circular RNA circ_0005230 Indicates Dismal Prognosis in Breast Cancer and Regulates Cell Proliferation and Invasion via miR-618/ CBX8 Signal Pathway

Abstract

Background/Aims: Circular RNAs (circRNAs) are a class of non-coding RNAs. They have been proved to be critically involved in tumorigenesis and progression of malignancies through competing endogenous RNA (ceRNA) mechanism. Nevertheless, the exploration between circRNAs and pathogenesis of breast cancer (BC) is limited. Previously, circ_0005230 was identified upregulated in BC tissues screened by circRNA microarray. In the present study, we aimed to investigate the expression pattern, functional role, and mechanism of circ_0005230 in BC. Methods: qRT-PCR was conducted to elucidate the expression levels of circ_0005230 in BC tissues and cells. Additionally, the clinical severity and prognostic value were investigated. CCK-8, colony-forming, flow cytometric assays were performed. Animal study was conducted to validate the in vitro data. What’s more, Transwell assays were induced to detect the cell metastatic properties of circ_0005230 exerts in BC cells. Luciferase reporter assay was used to measure the mechanism of circ_0005230. Results: circ_0005230 was overexpressed in BC tissue specimens and cell lines. The overexpression of circ_0005230 was related to adverse phenotypes in the patients with BC. In addition, circ_0005230 could be regarded as a prognostic predictor in BC patients. In vitro and in vivo data demonstrated the cell growth promoting role of circ_0005230. Moreover, circ_0005230 could also promote cell migratory and invasive capacities. For the mechanism investigation, circ_0005230 was proved to be a sponge of miR-618, and expression of miR-618 could regulate CBX8 expression via targeting the 3’UTR of CBX8. Rescue assays also illustrated an oncogenic function of circ_0005230 in BC via acting as a miR-618 sponge to promote CBX8 expression. Conclusion: circ_0005230/miR-618/CBX8 axis might play a key role in BC tumorigenesis and development.

Circular RNA circ-DONSON facilitates gastric cancer growth and invasion via NURF complex dependent activation of transcription factor SOX4

“…For example, circPVT1 contributes to non-small cell lung cancer (NSCLC) cell growth and migration by inhibiting miR-125b to activate E2F2 expression [13]. Circ_0005230 is overexpressed in breast cancer and promotes tumor cell division and invasiveness through miR-618/CBX8 signaling [14]. CircMMP9 is upregulated by EIF4A3 in glioblastoma and contributes to tumor development by sponging miR-124 [15].…”

Elevation of circular RNA circ_0005230 facilitates cell growth and metastasis via sponging miR-1238 and miR-1299 in cholangiocarcinoma

“…Previously, we identified circ_0005230 was elevated in breast cancer tissue samples and was linked to breast cancer patients’ unfavorable prognosis. Furthermore, the biological functions of circ_0005230 was partially attributed to its modulation on miR-618/CBX8 signaling [14]. Circ_0005230 is located at chr1:172109619-172113577 and is spliced from DNM3OS (DNM3 opposite strand/antisense RNA) gene (Fig.…”

Overexpression of circular RNA circ‐CDC45 facilitates glioma cell progression by sponging miR‐516b and miR‐527 and predicts an adverse prognosis

“…7 In this study, we found that upregulation of circ-CDC45 is related to larger tumor size and higher WHO grades. 8,9 For example, circ-NT5E served as a sponge against miR-422a to facilitate GM oncogenesis. In addition, we found that GM patients with elevated circ-CDC45 level displayed a shorter survival time than the patients with low expression, suggesting that circ-CDC45 may be a potential prognostic biomarker of GM.…”

“…5 The rapid development of RNA genomics has highlighted the oncogenic or anti-oncogenic role of circRNAs in many cancers, especially in GM. 8 For GM, circ_0034642 could facilitate tumorigenesis via the miR-1205/BATF3 axis, as reported by Yang et al 9 MicroRNAs (miRNAs) regulate downstream target expression at posttranscriptional level. 7 circ_0005230 functions as an efficient miR-518 sponge, thereby releasing the expression inhibition of CBX8 in breast cancer.…”

“…7 circ_0005230 functions as an efficient miR-518 sponge, thereby releasing the expression inhibition of CBX8 in breast cancer. 8 For GM, circ_0034642 could facilitate tumorigenesis via the miR-1205/BATF3 axis, as reported by Yang et al 9 MicroRNAs (miRNAs) regulate downstream target expression at posttranscriptional level. [10][11][12] Emerging studies suggest that miRNA is included in tumorigenesis.…”