Estrogen-induced circRNA, circPGR, functions as a ceRNA to promote estrogen receptor-positive breast cancer cell growth by regulating cell cycle-related genes

Wang, Lei; Jia, Yi; Lu, Lingyun; Zhang, Yueying; Wang, Lan; Hu, Guo-Sheng; Liu, Yichen; Ding, Jian; Shen, Hai‐feng; Zhao, Fangqing; Huang, Haihua; Li, Wen

doi:10.7150/thno.45302

Cited by 48 publications

(33 citation statements)

References 86 publications

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“…CircRNAs play as ceRNAs to regulate target gene expression through miRNAs [29,30]. For example, circPGR was recently found to function as a ceRNA to promote estrogen receptorpositive breast cancer cell growth [31]; our recent study found that hsa_circ_0001829 functions as an oncogene in GC and exerts its effects via miR-155-5p/SMAD2 axis [18]. In current study, results of knockdown and overexpression assays revealed that hsa_circ_0110389 regulates GC cells proliferation, migration and invasion in vitro, and animal studies showed that hsa_circ_0110389 silencing inhibited tumor growth in vivo.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA hsa_circ_0110389 promotes gastric cancer progression through upregulating SORT1 via sponging miR-127-5p and miR-136-5p

et al. 2021

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Increasing studies have found that circular RNAs (circRNAs) are aberrantly expressed and play important roles in the occurrence and development of human cancers. However, the function of circRNAs on environmental carcinogen-induced gastric cancer (GC) progression remains poorly elucidated. In the present study, hsa_circ_0110389 was identified as a novel upregulated circRNA in malignant-transformed GC cells through RNA-seq, and subsequent quantitative real-time PCR verified that hsa_circ_0110389 was significantly increased in GC tissues and cells. High hsa_circ_0110389 expression associates with advanced stages of GC and predicts poor prognosis. Knockdown and overexpression assays demonstrated that hsa_circ_0110389 regulates proliferation, migration, and invasion of GC cells in vitro. In addition, hsa_circ_0110389 was identified to sponge both miR-127-5p and miR-136-5p and SORT1 was validated as a direct target of miR-127-5p and miR-136-5p through multiple mechanism assays; moreover, hsa_circ_0110389 sponged miR-127-5p/miR-136-5p to upregulate SORT1 expression and hsa_circ_0110389 promoted GC progression through the miR-127-5p/miR-136-5p–SORT1 pathway. Finally, hsa_circ_0110389 knockdown suppressed GC growth in vivo. Taken together, our findings firstly identify the role of hsa_circ_0110389 in GC progression, which is through miR-127-5p/miR-136-5p–SORT1 pathway, and our study provides novel insight for the identification of diagnostic/prognostic biomarkers and therapeutic targets for GC.

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Section: Discussionmentioning

confidence: 99%

Circular RNA hsa_circ_0110389 promotes gastric cancer progression through upregulating SORT1 via sponging miR-127-5p and miR-136-5p

et al. 2021

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“…Several researches demonstrated that circRNAs could act as miRNA sponges ( Memczak et al, 2013 ; Yang et al, 2019 ; Zhou C. et al, 2020 ), and certain circRNAs with open reading frame (ORF) and internal ribosome entry site (IREs) acted as templates for protein translation ( Legnini et al, 2017 ; Yang et al, 2018 ; Zhang et al, 2018 ), while the circRNAs located in nucleus regulated expression of certain genes by interacting with RNA polymerase II ( Zhang et al, 2013 ; Li et al, 2015 ). In addition, circRNAs display powerful biological functions such as proliferation, migration, invasion and chemotherapy resistance in HER2-negative (HER2 – ) subtype of breast cancer ( Yang et al, 2019 ; Zhou Y. et al, 2020 ; Wang L. et al, 2021 ). Nevertheless, the role of circRNAs in regulating the cellular fate of HER2 + BC cells is rarely elucidated.…”

Section: Introductionmentioning

confidence: 99%

MiR-92b-3p Inhibits Proliferation of HER2-Positive Breast Cancer Cell by Targeting circCDYL

Liang

Ling

Lin

et al. 2021

Front. Cell Dev. Biol.

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ObjectivesCircular RNA (circRNA) is a novel class of RNA, which exhibits powerful biological function in regulating cellular fate of various tumors. Previously, we had demonstrated that over-expression of circRNA circCDYL promoted progression of HER2-negative (HER2–) breast cancer via miR-1275-ULK1/ATG7-autophagic axis. However, the role of circCDYL in HER2-positive (HER2+) breast cancer, in particular its role in modulating cell proliferation, one of the most important characteristics of cellular fate, is unclear.Materials and methodsqRT-PCR and in situ hybridization analyses were performed to examine the expression of circCDYL and miR-92b-3p in breast cancer tissues or cell lines. The biological function of circCDYL and miR-92b-3p were assessed by plate colony formation and cell viability assays and orthotopic animal models. In mechanistic study, circRNAs pull-down, RNA immunoprecipitation, dual luciferase report, western blot, immunohistochemical and immunofluorescence staining assays were performed.ResultsCircCDYL was high-expressed in HER2+ breast cancer tissue, similar with that in HER2– breast cancer tissue. Silencing HER2 gene had no effect on expression of circCDYL in HER2+ breast cancer cells. Over-expression of circCDYL promoted proliferation of HER2+ breast cancer cells but not through miR-1275-ULK1/ATG7-autophagic axis. CircRNA pull down and miRNA deep-sequencing demonstrated the binding of miR-92b-3p and circCDYL. Interestingly, circCDYL did not act as miR-92b-3p sponge, but was degraded in miR-92b-3p-dependent silencing manner. Clinically, expression of circCDYL and miR-92b-3p was associated with clinical outcome of HER2+ breast cancer patients.ConclusionMiR-92b-3p-dependent cleavage of circCDYL was an essential mechanism in regulating cell proliferation of HER2+ breast cancer cells. CircCDYL was proved to be a potential therapeutic target for HER2+ breast cancer, and both circCDYL and miR-92b-3p might be potential biomarkers in predicting clinical outcome of HER2+ breast cancer patients.

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“…Because of their unique characteristics and distinct advantages, such as their stability, long lifespan, time- and tissue-specific expression, they have turned into a novel hotspot in ncRNAs' research field to serve as potential biomarkers of cancer diagnosis and prognosis. CircRNAs are implicated in the immune response against tumors [ 20 ], amplification [ 21 ], invasion [ 22 ], and critical signaling pathways in BC [ 23 , 24 ], according to several reports. However, the function of circRNAs in BC cancer cells, is still largely unknown, and more investigations are required.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA hsa_circ_0044234 as distinct molecular signature of triple negative breast cancer: a potential regulator of GATA3

et al. 2021

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Background Circular RNAs (circRNAs) have been implicated in the initiation and development of breast cancer as functional non-coding RNAs (ncRNA). The roles of circRNAs as the competing endogenous RNAs (ceRNAs) to sponge microRNAs (miRNAs) have also been indicated. However, the functions of circRNAs in breast cancer have not been totally elucidated. This study aimed to explore the clinical implications and possible roles of circ_0044234 in carcinogenesis of the most problematic BC subtype, triple negative breast cancer (TNBC), which are in desperate need of biomarkers and targeted therapies. Methods The importance of circ_0044234 as one of the most dysregulated circRNAs in TNBC was discovered through microarray expression profile analysis. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to confirm the downregulation of circ_0044234 in triple negative tumors and cell lines versus non-triple negative ones. The bioinformatics prediction revealed that circ_0044234 could act as an upstream sponge in the miR-135b/GATA3 axis, two of the most dysregulated transcripts in TNBC. Results Our experimental investigation of circ_0044234 expressions in various BC subtypes as well as cell lines reveals that TNBC expresses circ_0044234 at a substantially lower level than non-TNBC. The ROC curve analysis indicates that it could be applied as a discriminative biomarker to identify TNBC from other BC subtypes. Moreover, circ_0044234 expression could be an independent prognostic biomarker in BC. Interestingly, a substantial inverse expression correlation was detected between circ_0044234 and miR-135b-5p as well as between miR-135b-5p and GATA3 in breast tumors. Conclusions The possible clinical usefulness of circ_0044234 as a promising distinct biomarker and upcoming therapeutic target for TNBC have been indicated in this research. Our comprehensive approach revealed the potential circ_0044234/miR135b-5p/GATA3 ceRNA axis in TNBC.

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Estrogen-induced circRNA, circPGR, functions as a ceRNA to promote estrogen receptor-positive breast cancer cell growth by regulating cell cycle-related genes

Cited by 48 publications

References 86 publications

Circular RNA hsa_circ_0110389 promotes gastric cancer progression through upregulating SORT1 via sponging miR-127-5p and miR-136-5p

Circular RNA hsa_circ_0110389 promotes gastric cancer progression through upregulating SORT1 via sponging miR-127-5p and miR-136-5p

MiR-92b-3p Inhibits Proliferation of HER2-Positive Breast Cancer Cell by Targeting circCDYL

Circular RNA hsa_circ_0044234 as distinct molecular signature of triple negative breast cancer: a potential regulator of GATA3

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