Circular RNA CircNOLC1, Upregulated by NF-KappaB, Promotes the Progression of Prostate Cancer via miR-647/PAQR4 Axis

Chen, Wenbin; Cen, Shengren; Zhou, Xumin; Yang, Taowei; Wu, Kuan-Hung; Zou, Libin; Luo, Junqi; Li, Chuanyin; Lv, Daojun; Mao, Xiangming

doi:10.3389/fcell.2020.624764

Cited by 37 publications

(23 citation statements)

References 39 publications

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“…For example, circRGPD6 inhibits cancer stem cell-regulated metastasis of breast cancer by the miR-26b/YAF2 signaling [ 24 ]. Meanwhile, circNOLC1 is enhanced by NF-kB, and induces prostate cancer development by miR-647/PAQR4 axis [ 15 ]. CircNOLC1 enhances progression and tumorigenesis of epithelial ovarian cancer by interacting ESRP1 and regulating RhoA and CDK1 expression [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

“…Zeng et al reported a circ-ANKS1B highly expressed in BC and closely related to advanced clinical stage and metastasis to lymph node [ 14 ]. CircNOLC1 was recently discovered to be overexpressed in prostate cancer by a microarray analysis, and affect prostate cancer cell proliferation and metastasis [ 15 ]. As critical cancer regulators, miRNAs participate in various biological processes during carcinogenesis via suppressing targeted mRNA translation [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

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The inhibition of circular RNA circNOLC1 by propofol/STAT3 attenuates breast cancer stem cells function via miR-365a-3p/STAT3 signaling

et al. 2021

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Background Breast cancer remains one of the most dreadful female malignancies globally, in which cancer stem cells (CSCs) play crucial functions. Circular RNAs have drawn great attention in cancer research area and propofol is a widely applied intravenous anesthetic agent. Methods: In the current study, we explored the function of circular RNA nucleolar and coiled-body phosphoprotein 1 (circNOLC1) in CSCs of breast cancer and the inhibitory impact of propofol on circNOLC1. Results The expression of circNOLC1 was induced in breast cancer tissues compared with the non-tumor tissues. The silencing of circNOLC1 was able to repress the viability of breast cancer cells. Meanwhile, the numbers of colony formation were suppressed by circNOLC1 knockdown in breast cancer cells. The inhibition of circNOLC1 reduced the invasion and migration ability of breast cancer cells. The mRNA and protein levels of E-cadherin were enhanced but Vimentin levels were reduced by the silencing of circNOLC1. The repression of circNOLC1 decreased the side population (SP) ratio in breast cancer cells. Meanwhile, the sphere formation ability of breast cancer cells was attenuated by the silencing of circNOLC1. The levels of ATP-binding cassette (ABC) superfamily G member 2 (ABCG2), c-Myc, B cell-specific Moloney murine leukemia virus integration site 1 (Bmi1), and SRY-box transcription factor 2 (Sox2) were repressed by the depletion of circNOLC1 in the cells. Regarding to the mechanism, circNOLC1 functioned as a competing endogenous RNAs (ceRNAs) for microRNA-365a-3p (miR-365a-3p) and the inhibition of miR-365a-3p rescued circNOLC1 depletion-repressed proliferation and cancer stem cell activity of breast cancer. MiR-365a-3p targeted signal transducer and activator of transcription 3 (STAT3) in breast cancer cells and circNOLC1 enhanced STAT3 expression by sponging miR-365a-3p. The overexpression of STAT3 could reverse miR-365a-3p or circNOLC1 depletion-inhibited proliferation and cancer stem cell properties of breast cancer. Interestingly, the expression of circNOLC1 and STAT3 was repressed by the treatment of propofol. The enrichment of STAT3 on circNOLC1 promoter was inhibited by propofol. The expression of circNOLC1 was suppressed by the silencing of STAT3 in the cells. The inhibition of circNOLC1 expression by propofol was rescued under the co-treatment of STAT3 overexpression. The overexpression of circNOLC1 rescued propofol-attenuated proliferation and cancer stem cell functions in vitro and in vivo. Conclusions Thus, we concluded that circNOLC1 contributes to CSCs properties and progression of breast cancer by targeting miR-365a-3p /STAT3 axis and propofol inhibited circNOLC1 by repressing STAT3 in a feedback mechanism.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The inhibition of circular RNA circNOLC1 by propofol/STAT3 attenuates breast cancer stem cells function via miR-365a-3p/STAT3 signaling

et al. 2021

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“…In previous studies, a number of circRNAs have been found to play critical roles in prostate cancer progression. For instance, circRNA nucleolar and coiled-body phosphoprotein 1, circRNA formin 1, circ-0016068, circ_0088233 and circ0005276 are all upregulated in prostate cancer and promote the development of prostate cancer ( Feng et al, 2019 ; Chen et al, 2020 ; Deng et al, 2020 ; Li et al, 2020 ; Shan et al, 2020 ). The findings of the present study extend the current understanding of the function of circRNAs in prostate cancer.…”

Section: Discussionmentioning

confidence: 99%

CircGNG4 Promotes the Progression of Prostate Cancer by Sponging miR-223 to Enhance EYA3/c-myc Expression

Lian

Zhang

et al. 2021

Front. Cell Dev. Biol.

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Patients diagnosed with prostate cancer often have a poor prognosis and limited treatment options, as the specific pathogenesis remains to be elucidated. Circular RNA (circRNA) is a type of non-coding RNA that interacts with microRNA (miRNA/miR) and transcription factors to regulate gene expression. However, little is known about specific circRNAs that serve roles in the pathogenesis of prostate cancer. Findings of the present study confirmed that circRNA G protein subunit γ 4 (circGNG4) was upregulated in prostate cancer tissues and cell lines. Knockdown of circGNG4 inhibited the malignant behavior of prostate cancer cells. Furthermore, bioinformatics were used to predict targeting interactions between circGNG4 or miR-223 and EYA transcriptional coactivator and phosphatase 3 (EYA3)/c-Myc mRNA. miR-223 inhibited the malignant behavior of prostate cancer cells, while EYA3/c-Myc had the opposite effect. circGNG4 enhanced the expression of EYA3/c-Myc by sponging miR-223 to promote the growth of prostate cancer tumors in vivo. In conclusion, the circGNG4/miR-223/EYA3/c-Myc regulatory pathway promoted the malignant progression of prostate cancer. The results of the present study may provide potential new targets for the diagnosis or treatment of prostate cancer.

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“…[15][16][17] Some studies have demonstrated that the expression of circRNAs is markedly dysregulated in tumor samples and widely involved in multiple types of human cancers. [18][19][20] These findings suggested that circRNAs might be an emerging and promising biomarker for the diagnosis and prognostic assessment of malignancies. Recently, a comprehensive microarray and RNA-Seq analysis identified a novel circRNA, has_circ_0000615, which was spliced from the ZNF609 gene, with the length of 874 nt.…”

Section: Introductionmentioning

confidence: 93%

The Diagnostic Value of Serum Exosomal Has_circ_0000615 for Breast Cancer Patients

Liu¹,

Peng²,

Liu³

et al. 2021

IJGM

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Background To explore the expression level of has_circ_0000615 in peripheral blood samples and evaluate its diagnostic value for breast cancer patients. Methods The peripheral blood samples of 95 breast cancer patients who underwent curative surgical resection and 95 age-matched healthy volunteers in our institutions from September 2019 to November 2020 were systematically collected. The expression level of has_circ_0000615 in the plasma was amplified and detected by qRT-PCR, and its correlation to clinicopathological characteristics of breast cancer patients were analyzed. Results Breast cancer patients had a significantly higher expression level of has_circ_0000615 in the plasma than healthy controls (P < 0.01), and its high expression was closely associated with advanced tumor stage (P=0.010), lymph node metastasis (P = 0.001) and high grade of recurrence risk (P=0.012). The receiver operator characteristic (ROC) curves showed that the area under curve (AUC) value, sensitivity and specificity of has_circ_0000615 for the diagnosis of non-metastatic breast cancer was 0.904 (95% CI: 0.863–0.944), 76.8% and 88.4%, respectively. Serum has_circ_0000615 expression had a better diagnostic efficiency than routine tumor biomarkers such as CA153, CA125 and CEA for distinguishing breast cancer patients from healthy individuals. TEM revealed that isolated exosomes from the culture medium of breast cancer cells had a disk-like appearance with a diameter of 80–200 nm vesicles, and the expression of exosome markers CD9 and CD81 was markedly increased. More importantly, the expression of has_circ_0000615 was detected in the exosomes and its expression level was markedly upregulated in breast cancer cell lines compared with normal ductal epithelial cells. The stability assay showed that there was no difference between RNA extraction at 0 hour and 24 hours in terms of the expression of has_circ_0000615 (P =0.327). Has_circ_0000615 might as exosomes be secreted into the circulating blood of breast cancer patients, resulting in a high expression level in plasma samples. Conclusion The detection of has_circ_0000615 might be a promising diagnostic method for breast cancer.

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Circular RNA CircNOLC1, Upregulated by NF-KappaB, Promotes the Progression of Prostate Cancer via miR-647/PAQR4 Axis

Cited by 37 publications

References 39 publications

The inhibition of circular RNA circNOLC1 by propofol/STAT3 attenuates breast cancer stem cells function via miR-365a-3p/STAT3 signaling

The inhibition of circular RNA circNOLC1 by propofol/STAT3 attenuates breast cancer stem cells function via miR-365a-3p/STAT3 signaling

CircGNG4 Promotes the Progression of Prostate Cancer by Sponging miR-223 to Enhance EYA3/c-myc Expression

The Diagnostic Value of Serum Exosomal Has_circ_0000615 for Breast Cancer Patients

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