Dataset Information

Circ_0008532 promotes bladder cancer progression by regulation of the miR-155-5p/miR-330-5p/MTGR1 axis.

ABSTRACT: BACKGROUND:Circular RNAs (circRNAs) have been associated with bladder cancer (BC), but the specific underlying molecular mechanism of their association with BC development has not been fully explored. METHODS:Levels of Circ_0008532, MTGR1 and miR-155-5p/miR-330-5p in bladder cancer cell lines and tissues were determined with quantitative real-time PCR and western blotting assays. In vitro and in vivo assays were performed to investigate the function of circ_0008532 in tumorigenesis in bladder cancer cells. The relationships of Circ_0008532, MTGR1 and miR-155-5p/miR-330-5p were predicted using bioinformatic tools and verified by RNA-FISH, RIP and luciferase assays. The effects of circ_0008532 on the Notch signaling pathway were determined by GSEA analysis and western blotting assay. RESULTS:We found that circ_0008532 is upregulated in BC cell lines and tissues. Moreover, overexpression of circ_0008532 promotes, and silencing of circ_0008532 inhibits the capacity for invasive in BC cells. In addition, circ_0008532 can directly interact with miR-155-5p and miR-330-5p as an miRNA sponge which mediates the expression of the miR-155-5p/miR-330-5p target gene MTGR1 and downstream Notch signaling. CONCLUSIONS:Circ_0008532 may act as an oncogene in BC through a novel circ_0008532/miR-155-5p, miR-330-5p /MTGR1/Notch pathway axis, which in turn may provide potential biomarkers and a therapeutic target for the management of bladder cancer.

SUBMITTER: Chen L

PROVIDER: S-EPMC7251916 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Circ_0008532 promotes bladder cancer progression by regulation of the miR-155-5p/miR-330-5p/MTGR1 axis.

Chen Liang L Yang Xiong X Zhao Jun J Xiong Ming M Almaraihah Raya R Chen Zhaohui Z Hou Teng T

Journal of experimental & clinical cancer research : CR 20200527 1

<h4>Background</h4>Circular RNAs (circRNAs) have been associated with bladder cancer (BC), but the specific underlying molecular mechanism of their association with BC development has not been fully explored.<h4>Methods</h4>Levels of Circ_0008532, MTGR1 and miR-155-5p/miR-330-5p in bladder cancer cell lines and tissues were determined with quantitative real-time PCR and western blotting assays. In vitro and in vivo assays were performed to investigate the function of circ_0008532 in tumorigenesi ...[more]

PMID: 32460831

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Project description:The aim of the present study was to explore the effects of LINC00649 on the proliferation, migration and invasion of bladder cancer (BC) and identify possible mechanisms. Through TCGA database analysis of LINC00649 expression in bladder cancer and the association of LINC00649 with the BC patient prognosis, RT‑qPCR was employed for detecting LINC00649 expression in 60 clinical tissue specimens and cell lines of bladder cancer. The lentivirus stable transfection or small interfering RNA was used to increase or decrease the LINC00649 expression level in T24 and UM‑UC‑3 cells. CCK8 and clone formation assay were utilized to observe the effects of LINC00649 on the proliferation and colony formation of BC cells. Transwell experiment was performed to detect the effects of LINC00649 on the migration and invasion of bladder cancer. Bioinformatics database was used to identify the possible downstream targets of LINC00649 while RT‑qPCR, western blot analysis and dual luciferase reporter gene experiments were carried out to verify the possible molecular mechanism. The TCGA database analysis revealed a significantly high expression of LINC00649 in bladder cancer and an association of LINC00649 expression with overall survival rate of BC patients. As shown by RT‑qPCR detection, LINC00649 expression was notably upregulated in BC tissues and BC cell lines. In addition, statistical analyses unveiled that highly expressed LINC00649 was clearly associated with poor overall survival of bladder cancer. Based on the in vitro cell experiment, upregulated LINC00649 considerately enhanced the proliferation, migration and invasion of BC cells, as opposed to those in T24 and UM‑UC‑3 cells by suppressing LINC00649. Mechanically, LINC00649 may promote the malignant progression of bladder cancer by regulating miR‑15a‑5p to promote the HMGA1 expression axis. Overall, LINC00649 upregulates HMGA1 expression by binding to miR‑15a‑5p to enhance the proliferation, migration and invasion of BC cells. Thus, LINC00649 is a potential biomarker and therapeutic target for bladder cancer.

Project description:BackgroundHepatocellular carcinoma (HCC) is the leading cause of tumor-related death worldwide due to high morbidity and mortality, yet lacking effective biomarkers and therapies. Circular RNAs (circRNAs) are a group of non-coding RNAs that regulate gene expression through interacting with miRNAs, implicating in the tumorigenesis and progression. A novel circRNA, circTP63, was reported to be an oncogene in HCC. However, its role in HCC remains unclear.MethodsqRT-PCR was used to assess the mRNA levels of CircTP63 in 90 pairs of tumor and adjacent normal tissues from HCC patients, one human normal hepatic epithelial cell line and HCC cell lines. CCK-8, colony formation, transwell, and flow cytometry assays were performed to detect the cellular function of circTP63/miR-155-5p/ZBTB18 in HCC cells. HCC xenograft mice models were established to assess the in vivo effect of circTP63. Bioinformatic analysis, RNA pull-down and luciferase assays were used to determine the interaction among circTP63/miR-155-5p/ZBTB18.ResultscircTP63 was significantly upregulated in HCC tissues and cell lines. High circTP63 expression is closely associated with the tumor stages, lymph node metastasis, and poor prognosis of HCC patients. Functionally, knockdown of circTP63 inhibited cell proliferation, migration, invasion, and promoted cell apoptosis of HCC. Meanwhile, overexpression of circTP63 enhanced HCC progression. Mechanically, circTP63 was a sponge of miR-155-5p to facilitate the ZBTB18 expression, and the ZBTB18 expression in HCC tissues was negatively associated with the survival rate of HCC patients. Furthermore, rescued assays revealed that the reduced tumor-promoting effect on HCC cells induced by knockdown of circTP63 can be reversed by miR-155-5p inhibitor or ZBTB18 overexpression.ConclusionOur data highlight a critical circTP63-miR-155-5p-ZBTB18 regulatory network involved in the HCC progression, gaining mechanistic insights into the function of circRNAs in HCC progression, and providing effective biomarkers and therapeutic targets for HCC treatment.

Dataset Information

Circ_0008532 promotes bladder cancer progression by regulation of the miR-155-5p/miR-330-5p/MTGR1 axis.

Publications

Circ_0008532 promotes bladder cancer progression by regulation of the miR-155-5p/miR-330-5p/MTGR1 axis.

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