<p>CircHIPK3 Promotes Clear Cell Renal Cell Carcinoma (ccRCC) Cells Proliferation and Metastasis via Altering of miR-508-3p/CXCL13 Signal</p>

Abstract

Introduction Accumulating evidence has demonstrated that circular RNAs (circRNAs) play a key role in the tumorigenesis of various types of cancers, including clear cell renal cell carcinoma (ccRCC). Materials and Methods Reverse transcription-quantitative polymerase chain reaction was used to detect the expression of circRNA homeodomain interacting protein kinase 3 (circHIPK3) and microRNAs (miRNAs), including miR-508-3p. The clinical measurement of circHIPK3 was evaluated by Kaplan–Meier survival analysis and receiver operating characteristic analysis. Cell Counting Kit-8 and Transwell chamber assays were performed to determine the changes in the proliferative and metastatic ability of A498 and 786-O cells. C-X-C motif chemokine ligand 13 (CXCL13) protein expression was detected by Western blot analysis. The targeted binding effect between miR-508-3p and circHIPK3 or CXCL13 was confirmed by constructed luciferase and RNA immunoprecipitation (RIP) assays, respectively. Fluorescence in situ hybridization (FISH) assay was used to measure the subcellular localization of circHIPK3 and miR-508-3p. Results It was found that circHIPK3 was markedly upregulated in ccRCC tissue and cell lines, and circHIPK3-upregulation was closely correlated with poor clinicopathological features in patients with ccRCC. It was found that both miR-508-3p and circHIPK3 were localized in the cytoplasm of ccRCC cells. The up- and downregulation of circHIPK3 positively regulated ccRCC cell proliferation and metastasis, and this regulatory effect was reversed by miR-508-3p. Through luciferase and RIP assays, it was confirmed that circHIPK3 could interacted with miR-508-3p. Furthermore, it was revealed that CXCL13, which was negatively correlated with miR-508-3p, was upregulated in ccRCC. It was also shown that CXCL13 was a downstream target of miR-508-3p. miR-508-3p suppressed ccRCC cell proliferation and metastasis by targeting CXCL13. Lastly, it was demonstrated that circHIPK3 promoted CXCL13 to facilitate ccRCC cell proliferation and metastasis by decoying miR-508-3p. Conclusion In brief, the results of the present study showed that circHIPK3 promoted ccRCC cell proliferation and metastasis by altering miR-5083p/CXCL13 signaling. The present findings might provide a novel target for the molecular treatment of ccRCC.

Circular RNA‐HIPK3 regulates human pulmonary artery endothelial cells function and vessel growth by regulating microRNA‐328‐3p/STAT3 axis

“…Studies have confirmed that circHIPK3 is located in the cytoplasm. 15 circRNA competitively binds to miRNAs and regulates the expression of downstream target genes when it is located in the cytoplasm. 16 MicroRNAs (miRNAs) are a class of small noncoding RNAs, including 20∼25 nucleotides, which regulate the expression levels of target genes by binding to the 3′-untranslated region (UTR) of mRNAs, degrading mRNAs, or inhibiting their translation process.…”

Non-coding RNA in cancer

“…In endothelial vessels, circ-CCAC1 up-regulates SH3GL2 by sequestering EZH2, thus reducing intercellular junction protein levels and increasing cell leakiness [48]. circRNAHIPK3 derived from exon 2 of HIPK3 gene is highly expressed in many types of cancer, including glioma [49], prostate cancer [50], breast cancer [51], colorectal cancer [52] and renal cancer [53]. Through screening of 424 miRNAs, 9 miRNAs showed great suppressive ability on the HIPK3 exon 2.…”

Emerging landscape of circHIPK3 and its role in cancer and other diseases (Review)

“…Li et al ( 107 ) found that the overexpression of circHIPK3 significantly inhibited RC cell invasion and migration in vitro , and it repressed proliferation of RC cells in vitro and in vivo . Additionally, another study by Han et al ( 108 ) demonstrated that circHIPK3 promoted clear cell RC cell proliferation and migration by altering miR-5083p/CXCL13 signaling, highlighting a potentially novel target for the molecular treatment of clear cell RC.…”