CircCSNK1G3 up‐regulates miR‐181b to promote growth and metastasis via TIMP3‐mediated epithelial to mesenchymal transitions in renal cell carcinoma

Abstract

Renal cell carcinoma (RCC) is the most common form of kidney cancer, with a high recurrence rate and metastasis capacity. Circular RNAs (circRNAs) have been suggested to act as the critical regulator in several diseases. This study is designed to investigate the role of circCSNK1G3 on RCC progression. We observed a highly expression of circCSNK1G3 in RCC tissues compared with normal tissues. The aberrantly circCSNK1G3 promoted the tumour growth and metastasis in RCC. In the subsequent mechanism investigation, we discovered that the tumour‐promoting effects of circCSNK1G3 were, at least partly, achieved by up‐regulating miR‐181b. Increased miR‐181b inhibits several tumour suppressor gene, including CYLD, LATS2, NDRG2 and TIMP3. Furthermore, the decreased TIMP3 leads to the enhanced epithelial to mesenchymal transition (EMT) process, thus promoting the cancer metastasis. In conclusion, we identified the oncogenic role of circCSNK1G3 in RCC progression and demonstrated the regulatory role of circCSNK1G3 induced miR‐181b expression, which leads to TIMP3‐mediated EMT process, thus resulting in tumour growth and metastasis in RCC. This study reveals the promise of circCSNK1G3 to be developed as a potential diagnostic and prognostic biomarker in the clinic. And the roles of circCSNK1G3 in cancer research deserve further investigation.

Circular RNAs as Prognostic Biomarkers in Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

“…One study was from Germany, two studies were from The Cancer Genome Atlas (TCGA) database, and other studies were from China. Together, 20 types of circRNAs were included in the meta-analysis (circHIAT1 ( Wang et al, 2017 ; Wang et al, 2019 ), circNUP98 ( Yu et al, 2020 ), circMYLK ( Li et al, 2020a ), hsa_circ_001895 ( Chen et al, 2020a ), circ‐EGLN3 ( Lin and Cai, 2020 ), circ_001842 ( Zeng et al, 2020 ), circ_0001368 ( Chen et al, 2020b ), cRAPGEF5 ( Chen et al, 2020c ), circ-ABCB10 ( Huang et al, 2019 ), circCSNK1G3 ( Li et al, 2021 ), circAKT1 ( Zhu et al, 2020 ), circAGAP1 ( Lv et al, 2021 ), circ_101341 ( Yue et al, 2020 ), circEHD2 ( Frey et al, 2021 ), circNETO2 ( Frey et al, 2021 ), ciRS-7 ( Zhao et al, 2020 ), hsa-hsa_circ_0085576 ( Liu et al, 2020a ), circTLK1 ( Li et al, 2020b ), circPTCH1 ( Liu et al, 2020b ), and circHIPK3 ( Han et al, 2020 )). Four circRNAs (circHIAT1, circ_0001368, cRAPGEF5, and circEHD2) were downregulated, and 16 circRNAs (circMYLK, hsa_circ_001895, circ-ABCB10, circAGAP1, circEHD2, hsa_circ_0085576, circTLK1, circPTCH1, circHIPK3, circNUP98, circ‐EGLN3, circ_001842, circCSNK1G3, circAKT1, and circ_101341) were upregulated.…”

Comprehensive analysis of PTEN‐related ceRNA network revealing the key pathways WDFY3‐AS2 ‐ miR‐21‐5p/miR‐221‐3p/miR‐222‐3p ‐ TIMP3 as potential biomarker in tumorigenesis and prognosis of kidney renal clear cell carcinoma

“…Tissue inhibitor of metalloproteinases 3 (TIMP3) is a member of the TIMP family and they are the main regulators of matrix metalloproteinases 49 . Overexpression of TIMP3 was shown to inhibit the proliferation and migration of a variety of malignant tumor cells, including colorectal cancer, 49 renal cell carcinoma, 50 and liver cancer 51 . Several studies have demonstrated the targeted regulation of TIMP3 by miR‐21‐5p, miR‐221‐3p, and miR‐222‐3p 52,53 .…”

A Four-MicroRNA Panel in Serum as a Potential Biomarker for Screening Renal Cell Carcinoma

“…In the study of RCC, TGF-β1 affected the expression of miR-181b-5p to regulate the proliferation and progression of RCC (Hanusek et al, 2022). Also, miR-181b-5p was upregulated by circular RNA circCSNK1G3 to promote tumor growth and metastasis in RCC via the TIMP3-mediated epithelial-to-mesenchymal transition (EMT) process (Li et al, 2021).…”