RNA-binding protein SORBS2 suppresses clear cell renal cell carcinoma metastasis by enhancing MTUS1 mRNA stability

Lv, Qi; Fan, Daiming; Zhou, Yong; Cai, Zhen; Wang, Gangmin

doi:10.1038/s41419-020-03268-1

Cited by 25 publications

(21 citation statements)

References 52 publications

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“…RBM14 encodes a ribonucleoprotein that functions as a general nuclear coactivator and an RNA splicing modulator in a PARP-dependent DSB repair process [ 29 ]. MTUS1 , a tumour-suppressor gene encoding angiotensin-II type 2 receptor-interacting proteins, is downregulated in clear cell renal cell carcinoma [ 31 ]. However, whether these mutations alter the clinical treatment of CDC patients remains unclear.…”

Section: Discussionmentioning

confidence: 99%

A genomic mutation spectrum of collecting duct carcinoma in the Chinese population

Zhang

Huang

et al. 2022

BMC Med Genomics

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Background Renal collecting duct carcinoma (CDC) is a rare and lethal subtype of renal cell carcinoma (RCC). The genomic profile of the Chinese population with CDC remains unclear. In addition, clinical treatments are contradictory. In this study, we aimed to identify the genomic mutation spectrum of CDC in the Chinese population. Methods Whole-exome sequencing was performed using the Illumina Novaseq™ 6000 platform. MuTect2 detects single-nucleotide variants (SNVs) and small scale insertions/deletions (INDELs). The identified mutations were annotated with ANNOVAR and validated by Sanger sequencing. Control-FREEC was used to detect copy number variation (CNV), and GISTIC was applied to detect frequently mutated altered regions. These data were compared with associated The Cancer Genome Atlas cohorts. Results Ten normal-matched CDC patients were included. The mean tumour mutation burden was 1.37 Mut/Mb. Six new recurrent somatic mutated genes were identified, including RBM14, MTUS1, GAK, DST, RNF213 and XIRP2 (20% and 2 of 10, respectively), and validated by Sanger sequencing. In terms of common mutated genes, SETD2 was altered in both CDC and other RCC subtypes but not in bladder urothelial carcinoma (BLCA); CDKN2A was a driver gene in both CDC (SNV: 10%, 1 of 10) and BLCA but not in other RCC subtypes. Next, 29 amplifications and 6 deletions of recurrent focal somatic CNVs were identified by GISTIC2.0, which displayed differences from kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP) and BLCA cohorts. Of note, CDKN2A (CNV alteration: 30%, 3 of 10) and CDKN2A-AS1 were the only overlapping genes of these four cohorts. Importantly, the CDKN2A mutation in our cohort differed from previous studies in urinary carcinomas. Moreover, CDKN2A-altered cases had significantly worse overall survival than wild-type cases in both KIRC and KIRP cohorts. In addition, the most frequently altered genomic pathway of our CDC cohort was the CDKN2A-mediated p53/RB1 pathway. Conclusions Our study offers the first genomic spectrum of the Chinese population with CDC, which differs from that of the Western population. The altered CDKN2A-mediated p53/RB1 pathway might provide new insight into potential therapeutic targets for CDC patients.

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Section: Discussionmentioning

confidence: 99%

A genomic mutation spectrum of collecting duct carcinoma in the Chinese population

Zhang

Huang

et al. 2022

BMC Med Genomics

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“…Over the last decade, RNA binding proteins (RBPs) have attracted growing attention in multiple diseases (31), particularly in tumors such as triple-negative breast cancer (32), clear cell renal cell carcinoma (33), and pancreatic cancer (34). RBPs also play a role in HCC (35)(36)(37)(38).…”

Section: Discussionmentioning

confidence: 99%

Prognostic prediction and gene regulation network of EIF2S2 in hepatocellular carcinoma based on data mining

Ji¹,

Wang²,

Cheng³

et al. 2021

J Gastrointest Oncol

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Background: Hepatocellular carcinoma (HCC) is a malignant tumor with a high fatality rate, predicting poor prognosis and therapeutic effect. Screening potential prognostic genes in HCC could be a creative way to advance clinical treatment. Eukaryotic translation initiation factor 2 subunit beta (EIF2S2) has reportedly been linked to several tumors, including liver cancer, but the prognostic predictions remain unknown.Therefore, we aimed to clarify the prognostic role and interaction network of EIF2S2 in HCC using bioinformatics data.Methods: We screened EIF2S2 using the Oncomine, Ualcan, and TCGA databases. R software was used to analyze the mRNA level and clinicopathological characteristics of hepatocellular carcinoma. Evaluation of the correlations between EIF2S2 and patients' survival was made using the Kaplan-Meier curves and Cox proportional hazards regression model. Then, the influence of EIF2S2 gene mutations on the prognosis of patients was explored by cBioPortal. The protein-protein interaction network of 50 similar genes related to EIF2S2 was implemented by GEPIA2 and Metascape. The LinkedOmics database allowed us to carry out Gene Set Enrichment Analysis. Finally, we constructed the EIF2S2 kinase, miRNA, and transcription factor target networks using GeneMANIA.Results: EIF2S2 mRNA was overexpressed in HCC and was closely associated with clinicopathological features, including gender, age, race, tumor grade, and stage. There was no correlation between EIF2S2 genetic mutations and prognostic survival. Combining Cox proportional hazards regression model analyses, high-expressed EIF2S2 predicted poor prognosis in HCC patients. Additionally, we screened the top three EIF2S2-related genes (PFDN4, HM13, and SNRPD1), the 50 similar genes, and then constructed a 50-similar-gene protein-protein interaction network identified by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways using Metascape. EIF2S2 target networks in HCC were identified in kinase, miRNA, and transcription factor networks, including the mitogen-activated protein kinase 1 (MAPK1), miRNAs (Mir-144), and transcription factors (GGAANCGGAANY_UNKNOWN) using GeneMANIA.Conclusions: EIF2S2 plays a crucial role in the gene-regulating network of HCC and may be a potential prognostic marker or therapeutic target for HCC patients.

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“…Furthermore, p53-regulation of ATIP1 transcripts suggested a link between MTUS1 gene regulation and cancer [ 18 ]. Indeed, MTUS1 down-regulation in cancer tissues was frequently reported, including in tumors from the breast [ 19 , 20 , 21 , 22 , 23 ], bladder [ 24 , 25 ], colon [ 26 , 27 , 28 , 29 ], gallbladder [ 30 ], gastric tissues [ 31 , 32 ], lung (NSCLC) [ 33 ], head-and-neck [ 34 , 35 , 36 , 37 , 38 , 39 ], clear cell renal cell carcinoma (cc-RCC) [ 40 , 41 ], and uveal melanoma [ 42 ], with the exception of prostate cancer, in which MTUS1 expression was reported to increase with cancer progression [ 43 , 44 ] ( Table 1 ). Only few studies were designed to discriminate between different ATIP isoforms, and they all pointed to ATIP3 as the major MTUS1 isoform altered in human malignancies [ 19 , 21 , 36 , 43 ], ATIP1 being a minor form expressed in normal peripheral tissues [ 14 ].…”

Section: Atip3 and The Mtus1 Gene A Historical Point Of Viewmentioning

confidence: 99%

“…In an independent study conducted in renal cancer cells, ATIP3 was found to regulate the phosphorylation of KIF2C (also designated MCAK), another microtubule depolymerizing kinesin of the KinI family. A recombinant fragment of ATIP3 was shown to contribute to KIF2C phosphorylation on serine 192 by Aurora kinase B, and increase tubulin polymerization, consistent with its microtubule stabilizing effects [ 40 ].…”

Section: Cancer-related Molecular Mechanisms Controlled By Atip3mentioning

confidence: 99%

“…Although this possibility has not been directly addressed in breast cancer, recent studies have indeed reported promoter methylation as a possible mechanism for MTUS1 down-regulation in non-small cell lung (NSCLC) carcinoma [ 33 ]. Another mechanism for regulation of MTUS1 mRNA stability by the RNA binding protein SORBS2 was recently reported in clear cell renal cell carcinoma [ 40 ]. Long non-coding RNAs were shown to control the stability of MTUS1 transcripts via microRNAs in gastric [ 32 ] and cervical cancer [ 63 ].…”

Section: Atip3 Is a Prognostic Biomarker In Breast Cancermentioning

confidence: 99%

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Microtubule-Associated Protein ATIP3, an Emerging Target for Personalized Medicine in Breast Cancer

Haykal

Rodrigues-Ferreira

Nahmias

2021

Cells

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Breast cancer is the leading cause of death by malignancy among women worldwide. Clinical data and molecular characteristics of breast tumors are essential to guide clinician’s therapeutic decisions. In the new era of precision medicine, that aims at personalizing the treatment for each patient, there is urgent need to identify robust companion biomarkers for new targeted therapies. This review focuses on ATIP3, a potent anti-cancer protein encoded by candidate tumor suppressor gene MTUS1, whose expression levels are markedly down-regulated in breast cancer. ATIP3 is a microtubule-associated protein identified both as a prognostic biomarker of patient survival and a predictive biomarker of breast tumors response to taxane-based chemotherapy. We present here recent studies pointing out ATIP3 as an emerging anti-cancer protein and a potential companion biomarker to be combined with future personalized therapy against ATIP3-deficient breast cancer.

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RNA-binding protein SORBS2 suppresses clear cell renal cell carcinoma metastasis by enhancing MTUS1 mRNA stability

Cited by 25 publications

References 52 publications

A genomic mutation spectrum of collecting duct carcinoma in the Chinese population

A genomic mutation spectrum of collecting duct carcinoma in the Chinese population

Prognostic prediction and gene regulation network of EIF2S2 in hepatocellular carcinoma based on data mining

Microtubule-Associated Protein ATIP3, an Emerging Target for Personalized Medicine in Breast Cancer

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