HIF1α-associated circDENND4C Promotes Proliferation of Breast Cancer Cells in Hypoxic Environment

Liang, Gehao; Liu, Zihao; Tan, Li Kuo; Su, An; Jiang, Wen Guo; Gong, Chang

doi:10.21873/anticanres.11827

Cited by 60 publications

(50 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, reports of this model in breast cancer are very limited. Tang et al revealed that circRNA-001982 promotes breast cancer cell carcinogenesis by decreasing miR-143 expression ( 39 ); Liang et al suggested that circRNA-DENND4C promoted the proliferation of breast cancer cells in a hypoxic environment ( 40 ). In this study, miR-449a showed a complementary sequence to circRNA-000911 based on bioinformatics analysis, and this miRNA was finally identified as the endogenous competing RNA by luciferase reporter assay and RIP assay.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive circular RNA profiling reveals the regulatory role of the circRNA-000911/miR-449a pathway in breast carcinogenesis

Wang

Xiao

et al. 2018

Int J Oncol

View full text Add to dashboard Cite

Circular RNAs (circRNAs) are key regulators in the development and progression of human cancers; however their roles in breast tumorigenesis are not yet well understood. Thus, the present study aimed to investigate the expression profiles and potential modulatory effects of circRNAs on breast carcinogenesis. A human circRNA microarray analysis was performed to screen for abnormally expressed circRNAs in breast cancer tissue and circRNA-000911 was identified as a circRNA which was significantly downregulated in breast cancer cells. Mechanistic investigations suggested that the enhanced expression of circRNA-000911 suppressed cell proliferation, migration and invasion, and promoted the apoptosis of breast cancer cells. By using a biotin-labeled circRNA-000911 probe to perform RNA precipitation in breast cancer cells, we identified miR-449a as the circRNA-000911-associated microRNA. Gain- and loss-of-function assays indicated that miR-449a antagonized circRNA-000911 to regulate breast cancer progression. Subsequently, Notch1 was identified as the functional target of miR-449a, and the overexpression of circRNA-000911 in breast cancer elevated Notch1 expression. Furthermore, Cignal Signal Transduction Reporter Array and western blot analysis identified nuclear factor-κB (NF-κB) signaling as a functional target of the circRNA-000911/miR-449a pathway. On the whole, our findings indicate that circRNA-000911 plays an anti-oncogenic role in breast cancer and may thus serve as a promising therapeutic target for patients with breast cancer. Therefore, the overexpression of circRNA-000911 may provide a future direction which may aid in the development of a novel treatment strategy for breast cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Comprehensive circular RNA profiling reveals the regulatory role of the circRNA-000911/miR-449a pathway in breast carcinogenesis

Wang

Xiao

et al. 2018

Int J Oncol

View full text Add to dashboard Cite

show abstract

“…For instance, circRNAs regulated by hypoxia in endothelial cells were identified for the first time [102]. Subsequently, in breast cancer cells, HIF1α was reported to be crucial for upregulating circDENND4C under hypoxic conditions, indicating that circDENND4C is an HIF1α-associated circRNA and promotes the proliferation of breast cancer cells [115] . Under hypoxia, loss-of-function experiments indicate that circDENND4C knockdown could suppress glycolysis, migration and invasion by increasing miR-200b and miR-200c in breast cancer cells [116].…”

Section: Hypoxia Regulates Circrna Productionmentioning

confidence: 99%

Roles of circRNAs in the tumour microenvironment

et al. 2020

View full text Add to dashboard Cite

The tumour microenvironment (TME) constitutes the area surrounding the tumour during its development and has been demonstrated to play roles in cancer-related diseases through crosstalk with tumour cells. Circular RNAs (circRNAs) are a subpopulation of endogenous noncoding RNAs (ncRNAs) that are ubiquitously expressed in eukaryotes and have multiple biological functions in the regulation of cancer onset and progression. An increasing number of studies have shown that circRNAs participate in the multifaceted biological regulation of the TME. However, details on the mechanisms involved have remained elusive until now. In this review, we analyse the effects of circRNAs on the TME from various perspectives, including immune surveillance, angiogenesis, hypoxia, matrix remodelling, exo-circRNAs and chemoradiation resistance. Currently, the enormous potential for circRNA use in targeted therapy and as noninvasive biomarkers have drawn our attention. We emphasize the prospect of targeting circRNAs as an essential strategy to regulate TME, overcome cancer resistance and improve therapeutic outcomes.

show abstract

“…There are currently few reports describing the role of circRNAs in breast cancer. Liang G et al reported that circDENND4C is a HIF1α-associated circRNA promoting the proliferation of breast cancer under hypoxia [ 3 ]. Lu L et al provided a profile of circRNAs in breast cancer and adjacent normal-appearing tissues [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

circGFRA1 and GFRA1 act as ceRNAs in triple negative breast cancer by regulating miR-34a

Liu

Xie

et al. 2017

J Exp Clin Cancer Res

277

230

View full text Add to dashboard Cite

BackgroudAccumulating evidences indicate that circular RNAs (circRNAs), a class of non-coding RNAs, play important roles in tumorigenesis. However, the function of circRNAs in triple negative breast cancer (TNBC) is largely unknown.MethodsWe performed circRNA microarrays to identify circRNAs that are aberrantly expressed in TNBC cell lines. Expression levels of a significantly upregulated circRNA, circGFRA1, was detected by quantitative real-time PCR (qRT-PCR) in TNBC cell lines and tissues. Kaplan-Meier survival analysis was used to explore the significance of circGFRA1 in clinical prognosis. Then, we examined the functions of circGFRA1 in TNBC by cell proliferation, apoptosis and mouse xenograft assay. In addition, luciferase assay was used to explore the miRNA sponge function of circGFRA1 in TNBC.ResultsMicroarray analysis and qRT-PCR verified a circRNA termed circGFRA1 that was upregulated in TNBC. Kaplan-Meier survival analysis showed that upregulated circGFRA1 was correlated with poorer survival. Knockdown of circGFRA1 inhibited proliferation and promoted apoptosis in TNBC. Via luciferase reporter assays, circGFRA1 and GFRA1 was observed to directly bind to miR-34a. Subsequent experiments showed that circGFRA1 and GFRA1 regulated the expression of each other by sponging miR-34a.ConclusionsTaken together, we conclude that circGFRA1 may function as a competing endogenous RNA (ceRNA) to regulate GFRA1 expression through sponging miR-34a to exert regulatory functions in TNBC. circGFRA1 may be a diagnostic biomarker and potential target for TNBC therapy.

show abstract

HIF1α-associated circDENND4C Promotes Proliferation of Breast Cancer Cells in Hypoxic Environment

Abstract: CircDENND4C is a HIF1α-associated circRNA promoting the proliferation of breast cancer cells under hypoxia.

Cited by 60 publications

References 11 publications

Comprehensive circular RNA profiling reveals the regulatory role of the circRNA-000911/miR-449a pathway in breast carcinogenesis

Comprehensive circular RNA profiling reveals the regulatory role of the circRNA-000911/miR-449a pathway in breast carcinogenesis

Roles of circRNAs in the tumour microenvironment

circGFRA1 and GFRA1 act as ceRNAs in triple negative breast cancer by regulating miR-34a

Contact Info

Product

Resources

About