Dataset Information

CircCEP128 Knockdown Suppresses Bladder Cancer Progression via Regulating microRNA-515-5p/SDC1 Axis.

ABSTRACT:

Background

Dysregulation of circular RNAs (circRNAs) is associated with bladder cancer progression. Nevertheless, the mechanisms of circRNA centrosomal protein 128 (circCEP128) underlying bladder cancer progression remain poorly understood.

Methods

The levels of circCEP128, microRNA-515-5p (miR-515-5p) and syndecan-1 (SDC1) were determined via reverse transcription-quantitative polymerase chain reaction or Western blot. The effects of circCEP128, miR-515-5p and SDC1 on bladder cancer progression were investigated via MTT and colony formation assays, flow cytometry and transwell analysis and subcutaneous xenograft experiments. The interactions between miR-515-5p and circCEP128 or SDC1 were examined through bioinformatics prediction and luciferase reporter assay.

Results

circCEP128 and SDC1 were highly expressed and miR-515-5p was low expressed in bladder cancer tissues and cells. circCEP128 knockdown hindered cell proliferation, migration and invasion and promoted cell apoptosis in bladder cancer. circCEP128 loss increased miR-515-5p expression through direct interaction in bladder cancer cells. MiR-515-5p depletion mitigated the influences of circCEP128 knockdown on bladder cancer cell phenotypes. SDC1 was a direct target of miR-515-5p. circCEP128 positively regulated SDC1 expression via miR-515-5p. MiR-515-5p restrained the malignant progression of bladder cancer cells by decreasing SDC1 expression. circCEP128 knockdown hindered the growth of bladder cancer xenograft tumors by up-regulating miR-515-5p and down-regulating SDC1.

Conclusion

circCEP128 knockdown hampered the tumorigenesis and progression of bladder cancer by regulating miR-515-5p/SDC1 axis in vitro and in vivo, deepening our understanding on the molecular mechanisms of circCEP128 in bladder cancer.

SUBMITTER: Cao G

PROVIDER: S-EPMC8020055 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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.