2. Academic Validation
  3. Characterization of circSCL38A1 as a novel oncogene in bladder cancer via targeting ILF3/TGF-β2 signaling axis

Characterization of circSCL38A1 as a novel oncogene in bladder cancer via targeting ILF3/TGF-β2 signaling axis

  • Cell Death Dis. 2023 Jan 25;14(1):59. doi: 10.1038/s41419-023-05598-2.
Peilong Li # 1 2,  Qi Mi # 1,  Suzhen Yan 1 2,  Yan Xie 1,  Zilian Cui 3,  Shujun Zhang 1,  Yifan Wang 1,  Huiru Gao 1,  Yunshan Wang 1 2 4,  Juan Li 5 6,  Lutao Du 7 8 9,  Chuanxin Wang 10 11 12 13
Affiliations

Affiliations

  • 1 Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, 250033, China.
  • 2 Shandong Engineering & Technology Research Center for Tumor Marker Detection, Jinan, Shandong, China.
  • 3 Department of Urology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, China.
  • 4 Shandong Provincial Clinical Medicine Research Center for Clinical Laboratory, Jinan, Shandong, China.
  • 5 Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, 250033, China. [email protected].
  • 6 Shandong Engineering & Technology Research Center for Tumor Marker Detection, Jinan, Shandong, China. [email protected].
  • 7 Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, 250033, China. [email protected].
  • 8 Shandong Engineering & Technology Research Center for Tumor Marker Detection, Jinan, Shandong, China. [email protected].
  • 9 Shandong Provincial Clinical Medicine Research Center for Clinical Laboratory, Jinan, Shandong, China. [email protected].
  • 10 Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, 250033, China. [email protected].
  • 11 Shandong Engineering & Technology Research Center for Tumor Marker Detection, Jinan, Shandong, China. [email protected].
  • 12 Shandong Provincial Clinical Medicine Research Center for Clinical Laboratory, Jinan, Shandong, China. [email protected].
  • 13 Shandong Technology Innovation Center for Big Data and Precision Medicine of Cancer, Jinan, 250033, Shandong, China. [email protected].
  • # Contributed equally.
PMID: 36697384 DOI: 10.1038/s41419-023-05598-2
Abstract

The regulatory role of circRNAs in Cancer metastasis has become a focused issue in recent years. To date, however, the discovery of novel functional circRNAs and their regulatory mechanisms via binding with RBPs in bladder Cancer (BC) are still lacking. Here, we screened out circSLC38A1 based on our sequencing data and followed validation with clinical tissue samples and cell lines. Functional assays showed that circSLC38A1 promoted BC cell invasion in vitro and lung metastasis of mice in vivo. By conducting RNA pull-down, mass spectrum, and RIP assays, circSLC38A1 was found to interact with Interleukin enhancer-binding factor 3 (ILF3), and stabilize ILF3 protein via modulating the ubiquitination process. By integrating our CUT&Tag-seq and RNA-seq data, TGF-β2 was identified as the functional target of the circSLC38A1-ILF3 complex. In addition, m6A methylation was enriched in circSLC38A1 and contributed to its upregulation. Clinically, circSLC38A1 was identified in serum exosomes of BC patients and could distinguish BC patients from healthy individuals with a diagnostic accuracy of 0.878. Thus, our study revealed an essential role and clinical significance of circSLC38A1 in BC via activating the transcription of TGF-β2 in an ILF3-dependent manner, extending the understanding of the importance of circRNA-mediated transcriptional regulation in BC metastasis.

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