CircRNA hsa_circ_0014130 function as a miR-132-3p sponge for playing oncogenic roles in bladder cancer via upregulating KCNJ12 expression

Li, Gang; Guo, Baoyin; Wang, Huadong; Gao-tong, Lin; Lan, Tianjie; Hua, Ying; Xu, Jian

doi:10.1007/s10565-021-09668-z

Cited by 25 publications

(12 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As oncogenes or tumor suppressors, circRNAs were discovered to be associated with BCa proliferation, migration and invasion [9]. For instance, hsa_circ_0014130 promotes BCa cell proliferation, migration and invasion by serving as a ceRNA for miR-132-3p [33]. CircNUDT21 upregulates MDM2 expression by acting as a miR-16-1-3p sponge to promote BCa proliferation and invasion [17].…”

Section: Discussionmentioning

confidence: 99%

CircHGS enhances the progression of bladder cancer by regulating the miR-513a-5p/VEGFC axis and activating the AKT/mTOR signaling pathway

et al. 2023

View full text Add to dashboard Cite

BackgroundBladder cancer (BCa) is a malignant tumor that occurs in the bladder mucosa with high mortality. Circular RNAs (circRNAs), newly discovered noncoding RNAs, are associated with the occurrence and development of BCa. However, the effects of circRNAs in BCa have not been fully elucidated. Through the GEO (Gene Expression Omnibus) database, an abnormally expressed circular RNA, circHGS (hsa_circ_0004721), was rst identi ed in BCa. In this study, we clari ed the roles and potential mechanism of circHGS in BCa progression. MethodsThe level of circHGS in tissue and cell was assessed by qRT-PCR. The proliferation, migration and invasion of BCa cells were detected by CCK8, colony formation assay, wound-healing assay, and Transwell assays, respectively. The interaction between circHGS/VEGFC and miR-513a-5p was detected by dual luciferase and qRT-PCR. VEGFC protein level was detected by western blotting. Nude mouse xenograft model was used to clarify the role of circHGS in tumor growth in vivo. ResultsCircHGS, originating from the HGS gene, is upregulated in BCa tissues compared to normal tissues.Functionally, silencing of circHGS apparently suppressed BCa cell proliferation, migration and invasion, but circHGS overexpression showed the opposite result. In vivo experiments also suggested that knockdown of circHGS suppressed tumor growth. Mechanistically, circHGS functions as a sponge of miR-513a-5p to elevate VEGFC expression and activate the AKT/mTOR signaling pathway, ultimately promoting BCa progression. ConclusionOur ndings indicated that circHGS promotes BCa progression via the miR-513a-5p/VEGFC/AKT/mTOR pathway and can be a promising therapeutic target of BCa.

show abstract

Section: Discussionmentioning

confidence: 99%

CircHGS enhances the progression of bladder cancer by regulating the miR-513a-5p/VEGFC axis and activating the AKT/mTOR signaling pathway

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Increasing evidence suggests that circRNA and circRNA-mediated ceRNA networks play a crucial role in the pathogenesis and progression of various cancers ( Zhong et al, 2018 ). For instance, hsa_circ_0014130 works as a sponge of miR-132-3p to advance the oncogenesis and metastasis of bladder cancer by regulating KCNJ12 expression ( Li et al, 2021 ), and circAGFG1 acts as a sponge of miR-195-5p to promote triple-negative breast cancer progression by regulating CCNE1 expression ( Yang et al, 2019 ). Here, to explore the underlying mechanisms of the circRNA-mediated ceRNA network involved in the occurrence and progression of WT, we constructed a circRNA-miRNA-mRNA ceRNA regulatory network based on sequencing data of clinical samples.…”

Section: Discussionmentioning

confidence: 99%

The Regulatory Network and Role of the circRNA-miRNA-mRNA ceRNA Network in the Progression and the Immune Response of Wilms Tumor Based on RNA-Seq

et al. 2022

View full text Add to dashboard Cite

Circular RNA (circRNA), which is a newly discovered non-coding RNA, has been documented to play important roles in miRNA sponges, and the dysregulation of which is involved in cancer development. However, circRNA expression profiles and their role in initiation and progression of Wilms tumor (WT) remain largely unclear at present. Here, we used paired WT samples and high-throughput RNA sequencing to identify differentially expressed circRNAs (DE-circRs) and mRNAs (DE-mRs). A total of 314 DE-circRs and 1612 DE-mRs were identified. The expression of a subset of differentially expressed genes was validated by qRT–PCR. A complete circRNA-miRNA-mRNA network was then constructed based on the common miRNA targets of DE-circRs and DE-mRs identified by miRanda prediction tool. The Gene set enrichment analysis (GSEA) indicated that several signaling pathways involving targeted DE-mRs within the ceRNA network were associated with cell cycle and immune response, which implies their participation in WT development to some extent. Subsequently, these targeted DE-mRs were subjected to implement PPI analysis and to identify 10 hub genes. Four hub genes were closely related to the survival of WT patients. We then filtered prognosis-related hub genes by Cox regression and least absolute shrinkage and selection operator (LASSO) regression analysis to construct a prognosis-related risk score system based on a three-gene signature, which showed good discrimination and predictive ability for WT patient survival. Additionally, we analyzed the mutational landscape of these genes and the associations between their expression levels and those of immune checkpoint molecules and further demonstrated their potential impact on the efficacy of immunotherapy. qRT–PCR and western blotting (WB) analysis were used to validate key differentially expressed molecules at the RNA and protein levels, respectively. Besides these, we selected a key circRNA, circEYA1, for function validation. Overall, the current study presents the full-scale expression profiles of circRNAs and the circRNA-related ceRNA network in WT for the first time, deepening our understanding of the roles and downstream regulatory mechanisms of circRNAs in WT development and progression. We further constructed a useful immune-related prognostic signature, which could improve clinical outcome prediction and guide individualized treatment.

show abstract

“…Thus, these findings suggest a critical role for the AKT pathway in the pathophysiological process of regeneration and revascularization of blood vessels in PWS. Interestingly, a recent study reported that KCNJ12 acts as a straightforward target of miR-132-3p to modulate the AKT signaling pathway in bladder cancer oncogenesis and metastasis ( 27 ). Therefore, it is possible that KCNJ12 mutation caused PWS pathology by activating the AKT pathway, targeting KCNJ12 or the AKT signaling pathway might be a candidate intervention in the treatment of this disease.…”

Section: Discussionmentioning

confidence: 99%

Whole-Genome Sequencing Identified KCNJ12 and SLC25A5 Mutations in Port-Wine Stains

Chen

Wang

et al. 2022

Front. Med.

View full text Add to dashboard Cite

Port-wine stains (PWSs) are a congenital capillary malformed disorder and are caused by a number of somatic mutations that disrupt vascular development. However, the underlying genetic mutations in the pathogenesis of PWS have not yet been fully elucidated. To understand PWS genetic variations and investigate novel genetic mutations, we extracted genomic DNA from four sporadic PWS patients and then performed whole-genome sequencing (WGS). Using Sorting Intolerant from Tolerant (SIFT), PolyPhen2, Mutation Assessor, MetaSVM to identify candidate genetic mutations and whole-exome sequencing (WES) to confirm the identified variants. We found a previously reported G protein subunit alpha q (GNAQ) mutation c.548G > A, p.Arg183Gln in one case, whereas no such mutation was found in the other three samples. Moreover, six novel somatic mutations in three genes, including KCNJ12, SLC25A5, POTEE, were found in these four samples. Importantly, WES also verified the KCNJ12 (c.433G > A, p.Gly145Ser) and SLC25A5 (c.413G > A, p.Arg138His) mutations in other five sporadic PWS patients, with the frequency of 60% (3 of 5) and 40% (2 of 5), respectively. Thus, we reveal in this study two novel somatic mutations, KCNJ12 and SLC25A5, in the sporadic PWS patients for the first time. These findings highlight the genetic polymorphism of PWS and provide potential clinical prediction targets for this disease.

show abstract

CircRNA hsa_circ_0014130 function as a miR-132-3p sponge for playing oncogenic roles in bladder cancer via upregulating KCNJ12 expression

Cited by 25 publications

References 33 publications

CircHGS enhances the progression of bladder cancer by regulating the miR-513a-5p/VEGFC axis and activating the AKT/mTOR signaling pathway

CircHGS enhances the progression of bladder cancer by regulating the miR-513a-5p/VEGFC axis and activating the AKT/mTOR signaling pathway

The Regulatory Network and Role of the circRNA-miRNA-mRNA ceRNA Network in the Progression and the Immune Response of Wilms Tumor Based on RNA-Seq

Whole-Genome Sequencing Identified KCNJ12 and SLC25A5 Mutations in Port-Wine Stains

Contact Info

Product

Resources

About