circKIF4A promotes tumorogenesis of glioma by targeting miR-139-3p to activate Wnt5a signaling

Abstract

Background: Glioma has the characteristics of high incidence and mortality, and is a common malignant tumor of the central nervous system. Circular RNAs (circRNAs) have been reported to play vital roles in progression of cancer including glioma, and circKIF4A is up-regulated in glioma tissues. However, its role and mechanisms in gliomas are unclear.Methods: circKIF4A and miR-139-3p were determined by qRT-PCR. Transwell assay, wound-healing assay, cell colony formation and flow cytometry were performed to measure cell invasion, migration, proliferation and apoptosis. Western blotting was used to evaluate Wnt/β-catenin pathway-related protein. Luciferase reporter assays confirmed the relationship among circKIF4A, miR-139-3p and Wnt5a. Sphere formation was performed to measure the ability of glioma-initiating cells (GICs) spheroid formation. A nude mouse xenograft model was established and immunohistochemical staining was used to detect Ki-67 and Wnt5a levels.Results: circKIF4A and Wnt5a were up-regulated and miR-139-3p was down-regulated in both glioma cells and tissues. circKIF4A promoted Wnt5a expression by sponging miR-139-3p. Knockdown of circKIF4A inhibited the colony formation ability, migration and invasion, and promoted the apoptosis of glioma cells by regulating miR-139-3p. Knockdown of circKIF4A inhibited Wnt/β-catenin signaling pathway and proliferation-related signal via miR-139-3p. Furthermore, knockdown of circKIF4A or overexpression of miR-139 suppressed the ability of sphere formation of GICs and inhibitd Wnt/β-catenin signaling pathway and proliferation-related signal in GICs. Additionally, depletion of circKIF4A decreased the expression level of Wnt5a and Ki-67, inhibited tumorigenesis in xenograft modes.Conclusion: circKIF4A was overexpressed in glioma, and knockdown of circKIF4A suppressed glioma progression via miR-139-3p/Wnt5a axis. The results indicated that circKIF4A may be a potential target for clinical treatment of glioma.

<p>microRNA-139-3p Inhibits Malignant Behaviors of Laryngeal Cancer Cells via the KDM5B/SOX2 Axis and the Wnt/β-Catenin Pathway</p>

“…In line with our findings, miR-139-3p overexpression suppressed Wnt/β-catenin signaling pathway in glioma. 37 Wnt1, a factor in the Wnt/β-catenin signaling, is demonstrated as a target of miR-139-5p in C2C12 myoblasts. 38 Additionally, Wnt/β-catenin pathway activation weakened the inhibition of miR-139-3p on LCA.…”

Upregulation of circ‑ASPH contributes to glioma cell proliferation and aggressiveness by targeting the miR‑599/AR/SOCS2‑AS1 signaling pathway

“…Recently, circRNAs have been clarified to regulate a number important processes, such as metastasis, differentiation and metabolism, leading to the progression of several diseases including malignant tumors (27). In previous studies, several circRNAs such as circ-FBXW7, circ-KIF4A and circ-TTBK2 have been proven to play essential functions in GM tumorigenesis (28)(29)(30). In the present study, a circRNA microarray was conducted to study the expression profile in GM.…”

<p>Hsa_circ_0003645 Promotes Breast Cancer Progression by Regulating miR-139-3p/HMGB1 Axis</p>

“…Previous research revealed that circRNA acts as a sponge of microRNA, which results in the loss of miRNA function, accompanied by an increased gene target. 40,41 As an essential class of non-coding small RNAs, microRNAs (miRNAs) could control target gene expression at the post-transcriptional level and play a critical role in the pathological processes, 42 which can be as a non-invasive biomarker for colorectal cancer, 43 an onco-suppressor for bladder cancer, cervical cancer and ovarian cancer. 25,44,45 Unusual expression of miRNAs is closely correlative to the development of glioma, which provides a potential therapeutic target for this disease.…”