The Circular RNA Interacts with STAT3, Increasing Its Nuclear Translocation and Wound Repair by Modulating Dnmt3a and miR-17 Function

Yang, Zhen-Guo; Awan, Faryal Mehwish; Du, William W.; Zeng, Yan; Lyu, Jingjing; Wu, De; Gupta, Shubham; Yang, Weining; Yang, Burton B.

doi:10.1016/j.ymthe.2017.05.022

Cited by 209 publications

(188 citation statements)

References 38 publications

(55 reference statements)

Supporting

Mentioning

187

Contrasting

Unclassified

Order By: Relevance

“…It has been reported that functionally the sponge and reservoir effects of circRNAs are opposite in that the sponge-type circRNAs may take away miRNAs from their targets while the reservoir-type circRNAs may help to maintain the miRNA levels and allow them to modulate their targets. There are several possibilities underlying these differences: one could be the miRNA-circRNA binding affinity and another could be the involvement of additional proteins (39,48). In that sense, the function as "sponge" and "reservoir" of circRNA may not be mutually exclusive.…”

Section: Discussionmentioning

confidence: 99%

ERβ-Mediated Alteration of circATP2B1 and miR-204-3p Signaling Promotes Invasion of Clear Cell Renal Cell Carcinoma

et al. 2018

View full text Add to dashboard Cite

Early studies have indicated that estrogen receptor beta (ERβ) can influence the progression of clear cell renal cell carcinoma (ccRCC). Here, we report the mechanistic details of ERβ-mediated progression of ccRCC. ERβ increased ccRCC cell invasion via suppression of circular RNA ATP2B1 (circATP2B1) expression by binding directly to the 5' promoter region of its host gene ATPase plasma membrane Ca2 transporting 1 (ATP2B1). ERβ-suppressed circATP2B1 then led to reduced miR-204-3p, which increased fibronectin 1 (FN1) expression and enhanced ccRCC cell invasion. Targeting ERβ with shRNA suppressed ccRCC metastasis in a murine model of RCC; adding circATP2B1 shRNA partly reversed this effect. Consistent with these experimental results, ccRCC patient survival data from The Cancer Genome Atlas indicated that a patient with higher ERβ and FN1 expression had worse overall survival and a patient with higher miR-204-3p expression had significantly better overall survival. Together, these results suggest that ERβ promotes ccRCC cell invasion by altering the ERβ/circATP2B1/miR-204-3p/FN1 axis and that therapeutic targeting of this newly identified pathway may better prevent ccRCC progression. These results identify an ERβ/circATP2B1/miR-204-3p/FN1 signaling axis in RCC, suggesting ERβ and circular RNA ATP2B1 as prognostic biomarkers for this disease. .

show abstract

Section: Discussionmentioning

confidence: 99%

ERβ-Mediated Alteration of circATP2B1 and miR-204-3p Signaling Promotes Invasion of Clear Cell Renal Cell Carcinoma

et al. 2018

View full text Add to dashboard Cite

show abstract

“…The first mechanism that was identified with regards to the role of circRNA was micro-RNA sponge [18]. In addition, circRNA could also bind with proteins in the related signal pathways [19][20][21][22]. While circRNAs can be translated to protein peptides [23,24], it is not known whether circRNA could regulate protein translation, especially the protein from their parental RNA.…”

Section: Introductionmentioning

confidence: 99%

Translation of yes-associated protein (YAP) was antagonized by its circular RNA via suppressing the assembly of the translation initiation machinery

et al. 2019

Self Cite

View full text Add to dashboard Cite

Yap is the key component of Hippo pathway which plays crucial roles in tumorigenesis. Inhibition of Yap activity could promote apoptosis, suppress proliferation, and restrain metastasis of cancer cells. However, how Yap is regulated is not fully understood. Here, we reported Yap being negatively regulated by its circular RNA (circYap) through the suppression of the assembly of Yap translation initiation machinery. Overexpression of circYap in cancer cells significantly decreased Yap protein but did not affect its mRNA levels. As a consequence, it remarkably suppressed proliferation, migration and colony formation of the cells. We found that circYap could bind with Yap mRNA and the translation initiation associated proteins, eIF4G and PABP. The complex containing overexpressed circYap abolished the interaction of PABP on the poly(A) tail with eIF4G on the 5′-cap of the Yap mRNA, which functionally led to the suppression of Yap translation initiation. Individually blocking the binding sites of circYap on Yap mRNA or respectively mutating the binding sites for PABP and eIF4G derepressed Yap translation. Significantly, breast cancer tissue from patients in the study manifested dysregulation of circYap expression. Collectively, our study uncovered a novel molecular mechanism in the regulation of Yap and implicated a new function of circular RNA, supporting the pursuit of circYap as a potential tool for future cancer intervention.

show abstract

“…This interacted complex can impact on cell proliferation and cell cycle regulation [58]. In addition, most recent studies also highlight that circ-Amotl1 can determine the subcellular translocation of several RBPs, such as pyruvate dehydrogenase kinase 1 (PDK1), MYC, and signal transducer and activator of transcription 3 (STAT3) [59][60][61].…”

Section: Interaction With Rbpsmentioning

confidence: 99%

Circular RNAs in the tumour microenvironment

Shuai

Gao

et al. 2020

Mol Cancer

View full text Add to dashboard Cite

Background: Circular RNAs (circRNAs) are a new class of endogenous non-coding RNAs (ncRNAs) widely expressed in eukaryotic cells. Mounting evidence has highlighted circRNAs as critical regulators of various tumours. More importantly, circRNAs have been revealed to recruit and reprogram key components involved in the tumour microenvironment (TME), and mediate various signaling pathways, thus affecting tumourigenesis, angiogenesis, immune response, and metastatic progression.Main body of the abstract: In this review, we briefly introduce the biogenesis, characteristics and classification of circRNAs, and describe various mechanistic models of circRNAs. Further, we provide the first systematic overview of the interplay between circRNAs and cellular/non-cellular counterparts of the TME and highlight the potential of circRNAs as prospective biomarkers or targets in cancer clinics. Finally, we discuss the biological mechanisms through which the circRNAs drive development of resistance, revealing the mystery of circRNAs in drug resistance of tumours. Short conclusion:Deep understanding the emerging role of circRNAs and their involvements in the TME may provide potential biomarkers and therapeutic targets for cancer patients. The combined targeting of circRNAs and co-activated components in the TME may achieve higher therapeutic efficiency and become a new mode of tumour therapy in the future.

show abstract

The Circular RNA Interacts with STAT3, Increasing Its Nuclear Translocation and Wound Repair by Modulating Dnmt3a and miR-17 Function

Cited by 209 publications

References 38 publications

ERβ-Mediated Alteration of circATP2B1 and miR-204-3p Signaling Promotes Invasion of Clear Cell Renal Cell Carcinoma

ERβ-Mediated Alteration of circATP2B1 and miR-204-3p Signaling Promotes Invasion of Clear Cell Renal Cell Carcinoma

Translation of yes-associated protein (YAP) was antagonized by its circular RNA via suppressing the assembly of the translation initiation machinery

Circular RNAs in the tumour microenvironment

Contact Info

Product

Resources

About