Generation and Application of Inducible Chimeric RNA ASTN2-PAPPAas Knockin Mouse Model

Luo, Yichen; Du, Liqun; Yao, Ziting; Fan, Lida; Li, Feifei; Zhu, Jianlin; Coppes, Robert P.; Zhang, Dianzheng; Pan, Yunlong; Gao, Shegan; Zhang, Hao

doi:10.3390/cells11020277

Cited by 1 publication

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References 26 publications

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“…For example, the first discovered gene fusion, BCR-ABL in chronic myeloid leukemia (AML) [ 13 ], the famous oncogenic fusion, TMPRSS2-ERG in prostate cancer [ 14 ], and EML4-ALK in lung adenocarcinomas [ 15 ], etc. Chimeric RNAs can be products due to chromosomal rearrangement as the well-known examples listed above, but they can also be generated due to intergenic splicing such as SLC45A3-ELK4 in prostate cancer [ 16 ], ASTN2-PAPPA antisense in esophageal cancer [ 17 ], and BCL2L2-PABPN1 in bladder cancer [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Profile of chimeric RNAs and TMPRSS2-ERG e2e4 isoform in neuroendocrine prostate cancer

et al. 2022

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Purpose Specific gene fusions and their fusion products (chimeric RNA and protein) have served as ideal diagnostic markers and therapeutic targets for cancer. However, few systematic studies for chimeric RNAs have been conducted in neuroendocrine prostate cancer (NEPC). In this study, we explored the landscape of chimeric RNAs in different types of prostate cancer (PCa) cell lines and aimed to identify chimeric RNAs specifically expressed in NEPC. Methods To do so, we employed the RNA-seq data of eight prostate related cell lines from Cancer Cell Line Encyclopedia (CCLE) for chimeric RNA identification. Multiple filtering criteria were used and the candidate chimeric RNAs were characterized at multiple levels and from various angles. We then performed experimental validation on all 80 candidates, and focused on the ones that are specific to NEPC. Lastly, we studied the clinical relevance and effect of one chimera in neuroendocrine process. Results Out of 80 candidates, 15 were confirmed to be expressed preferentially in NEPC lines. Among them, 13 of the 15 were found to be specifically expressed in NEPC, and four were further validated in another NEPC cell line. Importantly, in silico analysis showed that tumor malignancy may be correlated to the level of these chimeric RNAs. Clinically, the expression of TMPRSS2-ERG (e2e4) was elevated in tumor tissues and indicated poor clinical prognosis, whereas the parental wild type transcripts had no such association. Furthermore, compared to the most frequently detected TMPRSS2-ERG form (e1e4), e2e4 encodes 31 more amino acids and accelerated neuroendocrine process of prostate cancer. Conclusions In summary, these findings painted the landscape of chimeric RNA in NEPC and supported the idea that some chimeric RNAs may represent additional biomarkers and/or treatment targets independent of parental gene transcripts.

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