Molecular mechanisms of non-genetic aberrant peptide production in cancer

Moolgavkar SH, Knudson AG Jr. Mutation and cancer: a model for human carcinogenesis. J Natl Cancer Inst. 1981;66:1037–52.

Article  CAS  PubMed  Google Scholar 

Piazzi M, Bavelloni A, Salucci S, Faenza I, Blalock WL. Alternative splicing, RNA editing, and the current limits of next generation sequencing. Genes. 2023;14:1386.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bonnal SC, López-Oreja I, Valcárcel J. Roles and mechanisms of alternative splicing in cancer - implications for care. Nat Rev Clin Oncol. 2020;17:457–74.

Article  PubMed  Google Scholar 

Frezza V, Chellini L, Del Verme A, Paronetto MP. RNA editing in cancer progression. Cancers. 2023;15:5277.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tang SJ, Shen H, An O, Hong H, Li J, Song Y, et al. Cis- and trans-regulations of pre-mRNA splicing by RNA editing enzymes influence cancer development. Nat Commun. 2020;11:799.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kjer-Hansen P, Weatheritt RJ. The function of alternative splicing in the proteome: rewiring protein interactomes to put old functions into new contexts. Nat Struct Mol Biol. 2023;30:1844–56.

Article  CAS  PubMed  Google Scholar 

Bradley RK, Anczuków O. RNA splicing dysregulation and the hallmarks of cancer. Nat Rev Cancer. 2023;23:135–55.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wu S, Huang Y, Zhang M, Gong Z, Wang G, Zheng X, et al. ASCancer Atlas: a comprehensive knowledgebase of alternative splicing in human cancers. Nucleic Acids Res. 2023;51:D1196–d204.

Article  CAS  PubMed  Google Scholar 

Park S, Brugiolo M, Akerman M, Das S, Urbanski L, Geier A, et al. Differential functions of splicing factors in mammary transformation and breast cancer metastasis. Cell Rep. 2019;29:2672–88.e7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Song X, Wan X, Huang T, Zeng C, Sastry N, Wu B, et al. SRSF3-regulated RNA alternative splicing promotes glioblastoma tumorigenicity by affecting multiple cellular processes. Cancer Res. 2019;79:5288–301.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li Y, Chen Z, Peng J, Yuan C, Yan S, Yang N, et al. The splicing factor SNRPB promotes ovarian cancer progression through regulating aberrant exon skipping of POLA1 and BRCA2. Oncogene. 2023;42:2386–401.

Article  CAS  PubMed  Google Scholar 

Angiolini F, Belloni E, Giordano M, Campioni M, Forneris F, Paronetto MP, et al. A novel L1CAM isoform with angiogenic activity generated by NOVA2-mediated alternative splicing. Elife. 2019;8:e44305.

Article  PubMed  PubMed Central  Google Scholar 

Jbara A, Lin KT, Stossel C, Siegfried Z, Shqerat H, Amar-Schwartz A, et al. RBFOX2 modulates a metastatic signature of alternative splicing in pancreatic cancer. Nature. 2023;617:147–53.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Maurin M, Ranjouri M, Megino-Luque C, Newberg JY, Du D, Martin K, et al. RBFOX2 deregulation promotes pancreatic cancer progression and metastasis through alternative splicing. Nat Commun. 2023;14:8444.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Aguirre AJ, Hahn WC. Synthetic lethal vulnerabilities in KRAS-mutant cancers. Cold Spring Harb Perspect Med. 2018;8:a031518.

Article  PubMed  PubMed Central  Google Scholar 

Escobar-Hoyos LF, Penson A, Kannan R, Cho H, Pan CH, Singh RK, et al. Altered RNA splicing by mutant p53 activates oncogenic RAS signaling in pancreatic cancer. Cancer Cell. 2020;38:198–211.e8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Vigil D, Cherfils J, Rossman KL, Der CJ. Ras superfamily GEFs and GAPs: validated and tractable targets for cancer therapy? Nat Rev Cancer. 2010;10:842–57.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang S, Bao Y, Shen X, Pan Y, Sun Y, Xiao M, et al. RNA binding motif protein 10 suppresses lung cancer progression by controlling alternative splicing of eukaryotic translation initiation factor 4H. EBioMedicine. 2020;61:103067.

Article  PubMed  PubMed Central  Google Scholar 

Wheeler EC, Vora S, Mayer D, Kotini AG, Olszewska M, Park SS, et al. Integrative RNA-omics discovers GNAS alternative splicing as a phenotypic driver of splicing factor-mutant neoplasms. Cancer Discov. 2022;12:836–55.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jones PA, Taylor SM. Cellular differentiation, cytidine analogs and DNA methylation. Cell. 1980;20:85–93.

Article  CAS  PubMed  Google Scholar 

Zong L, Hattori N, Yasukawa Y, Kimura K, Mori A, Seto Y, et al. LINC00162 confers sensitivity to 5-Aza-2′-deoxycytidine via modulation of an RNA splicing protein, HNRNPH1. Oncogene. 2019;38:5281–93.

Article  CAS  PubMed  Google Scholar 

Zhang F, Wang H, Yu J, Yao X, Yang S, Li W, et al. LncRNA CRNDE attenuates chemoresistance in gastric cancer via SRSF6-regulated alternative splicing of PICALM. Mol Cancer. 2021;20:6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zeng J, Xu H, Huang C, Sun Y, Xiao H, Yu G, et al. CD46 splice variant enhances translation of specific mRNAs linked to an aggressive tumor cell phenotype in bladder cancer. Mol Ther Nucleic Acids. 2021;24:140–53.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Birladeanu AM, Rogalska M, Potiri M, Papadaki V, Andreadou M, Kontoyiannis DL, et al. The scaffold protein IQGAP1 links heat-induced stress signals to alternative splicing regulation in gastric cancer cells. Oncogene. 2021;40:5518–32.

Article  CAS  PubMed  Google Scholar 

Ahuja N, Ashok C, Natua S, Pant D, Cherian A, Pandkar MR, et al. Hypoxia-induced TGF-β-RBFOX2-ESRP1 axis regulates human MENA alternative splicing and promotes EMT in breast cancer. NAR Cancer. 2020;2:zcaa021.

Article  PubMed  PubMed Central  Google Scholar 

López-Pérez A, Remeseiro S, Hörnblad A. Diet-induced rewiring of the Wnt gene regulatory network connects aberrant splicing to fatty liver and liver cancer in DIAMOND mice. Sci Rep. 2023;13:18666.

Article  PubMed  PubMed Central  Google Scholar 

North K, Benbarche S, Liu B, Pangallo J, Chen S, Stahl M, et al. Synthetic introns enable splicing factor mutation-dependent targeting of cancer cells. Nat Biotechnol. 2022;40:1103–13.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dvinge H, Kim E, Abdel-Wahab O, Bradley RK. RNA splicing factors as oncoproteins and tumour suppressors. Nat Rev Cancer. 2016;16:413–30.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nagel R, Pataskar A, Champagne J, Agami R. Boosting antitumor immunity with an expanded neoepitope landscape. Cancer Res. 2022;82:3637–49.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pan Y, Phillips JW, Zhang BD, Noguchi M, Kutschera E, McLaughlin J, et al. IRIS: discovery of cancer immunotherapy targets arising from pre-mRNA alternative splicing. Proc Natl Acad Sci USA. 2023;120:e2221116120.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kim GB, Fritsche J, Bunk S, Mahr A, Unverdorben F, Tosh K, et al. Quantitative immunopeptidomics reveals a tumor stroma-specific target for T cell therapy. Sci Transl Med. 2022;14:eabo6135.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bowling EA, Wang JH, Gong F, Wu W, Neill NJ, Kim IS, et al. Spliceosome-targeted therapies trigger an antiviral immune response in triple-negative breast cancer. Cell. 2021;184:384–403.e21.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lu SX, De Neef E, Thomas JD, Sabio E, Rousseau B, Gigoux M, et al. Pharmacologic modulation of RNA splicing enhances anti-tumor immunity. Cell. 2021;184:4032–47.e31.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bland P, Saville H, Wai PT, Curnow L, Muirhead G, Nieminuszczy J, et al. SF3B1 hotspot mutations confer sensitivity to PARP inhibition by eliciting a defective replication stress response. Nat Genet. 2023;55:1311–23.

Article  CAS 

Comments (0)

No login
gif