Silencing circular RNA circ_0054537 and upregulating microRNA-640 suppress malignant progression of renal cell carcinoma via regulating neuronal pentraxin-2 (NPTX2)

ABSTRACT

Hsa_circ_0054537 (circ_0054537) is a novel tumor-related circular RNA in renal cell carcinoma (RCC), and we intended to ascertain its dysregulation and functions in RCC malignant progression, as well as the underlying mechanism via serving as competing endogenous RNA (ceRNA). In this research, using real-time quantitative PCR, we found circ_0054537 was upregulated in RCC tissues and cells, and distributed throughout the cytoplasm. Then, functional effects of circ_0054537 in RCC were detected using cell counting kit-8, transwell, flow cytometry and glycolysis stress test and adenosine Triphosphate (ATP) assays. The results uncovered that circ_0054537 knockdown inhibited cell proliferation, migration, invasion, autophagy and glycolysis, but promoted apoptosis in RCC cells. Notably, circ_0054537 was identified as a ceRNA for microRNA (miR)-640, and miR-640 could target neuronal pentraxin-2 (NPTX2), as evidenced by dual-luciferase reporter assay and RNA immunoprecipitation assay. Besides, miR-640 downregulation or NPTX2 overexpression partly overturned the tumor suppressor function of circ_0054537 silence and miR-640 overexpression in RCC cells. Additionally, RCC cell growth in vivo was retarded by circ_0054537 silence. In conclusion, circ_0054537/miR-640/NPTX2 ceRNA pathway regulated RCC malignant progression in vitro and curbed RCC tumor growth in vivo, which could be a potential diagnosis and therapeutic target of RCC.

KEYWORDS:

• Circ_0054537
• miR-640
• NPTX2
• RCC

Highlights

1. Circ_0054537, miR-640, and NPTX2 were abnormally expressed in RCC tissues and cells.

2. Circ_0054537 silence constrained RCC malignant progression in vitro and in vivo.

3. Circ_0054537 could regulate miR-640/NPTX2 interaction via competing endogenous RNA mechanism.

Ethics Approval and Consent to Participate

The design of this protocol follows the tenets of the Declaration of Helsinki, approved by the Ethics Committee of The Fourth Hospital of Hebei Medical University.

Disclosure statement

The authors declare that they have no financial conflicts of interest

Ethics Approval and Consent to Participate

The design of this protocol follows the tenets of the Declaration of Helsinki, approved by the Ethics Committee of The Fourth Hospital of Hebei Medical University.

Data availability statement

All data generated or analysed during this study are included in this published article (and its supplementary information files).

Supplementary material

Supplemental data for this article can be accessed here

Additional information

Funding

There is no funding to report.