Cancer-related micropeptides encoded by ncRNAs: Promising drug targets and prognostic biomarkers

Setrerrahmane, Sarra; Li, Mengwei; Zoghbi, Abdelmoumin; Lv, Xue; Zhang, Sen; Zhao, Wenjing; Lu, Jingjing; Craik, David J.; Xu, Hanmei

doi:10.1016/j.canlet.2022.215723

Cited by 31 publications

(13 citation statements)

References 170 publications

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“…Are these nonC-TL relevant cancer antigens? It is becoming increasingly clear that many of the uORFs, 5′UTRs, and ncRNAs unexpectedly code for peptides associated with malignant processes, providing a basis for their presence in cancer and strengthening the rationale for developing therapies that target these peptides ( 18 ). Some of these nonC-TL might be compared with truncal cancer neoantigens that are driver mutations for cancer development.…”

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confidence: 99%

Cancer's Dark Matter: Lighting the Abyss Unveils Universe of New Therapies

Fox

Urba

Jensen

et al. 2023

Clinical Cancer Research

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mentioning

confidence: 99%

Cancer's Dark Matter: Lighting the Abyss Unveils Universe of New Therapies

Fox

Urba

Jensen

et al. 2023

Clinical Cancer Research

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“…Recent accumulating evidence con rmed that non-coding RNAs and their encoded proteins can serve as novel potential therapeutic targets for various types of carcinomas 32,33,34 . For instance, Li et al demonstrated that the MIAC micropeptide encoded by an lncRNA inhibits the progression and metastasis of renal carcinoma by deactivating the EGEG/EGFR signaling pathway 35 .…”

Section: Discussionmentioning

confidence: 99%

The DDUP protein encoded by the DNA damage-induced CTBP1-DT lncRNA confers chemoresistance in ovarian cancer

Lang

Qing

Wei

et al. 2023

Preprint

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Aberrant DNA damage response (DDR) signaling is one of major reasons underlying chemotherapy failure in cancer, and understanding the mechanism underlying aberrant DDR signaling would aid in developing novel strategies for overcoming cancer chemoresistance. The present study demonstrated that the expression of the DDUP microprotein, encoded by the CTBP1-DT lncRNA, increased in chemotherapy non-response ovarian cancer cells and was inversely correlated to platinum-based chemotherapy response. Using a patient-derived human cancer cell model, we observed that the formation of DDUP foci, which is induced by DNA damage, played an important role in platinum-based chemotherapy resistance through dual RAD51C-mediated homologous recombination (HR) and proliferating cell nuclear antigen (PCNA)-mediated post-replication repair (PRR) mechanisms. These mechanisms are mediated via interactions with RAD18/RAD51C and RAD18/PCNA complexes at the sites of DNA damage and sustained RAD18-mediated DNA damage signaling. Notably, treatment with an ATR inhibitor disrupted the DDUP/RAD18 interaction and abolished the effect of DDUP on prolonged DNA damage signaling, which resulted in the hypersensitivity of ovarian cancer cells to platinum-based chemotherapy in vivo. Altogether, the study provides insights into DDUP-mediated aberrant DDR signaling in cancer chemoresistance and describes a potential novel therapeutic approach for the management of platinum-resistant ovarian cancer.

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“…With the advancement of multi-omics next-generation sequencing (such as ribosomal mapping and protein/peptide omics) and computational biology, continuous evidences [ 1 – 3 ] revealed the existence of small open reading frame (sORF) within non-coding RNAs (such as lncRNA, circRNA, pri-miRNA), 5'UTR, 3'UTR, antisense transcripts, intergeneric non-coding regions, etc. These sORFs can produce functional micropeptides participating in the regulation of biological processes such as muscle development [ 4 ], energy metabolism [ 5 ], immune regulation [ 6 ], and tumor development [ 7 , 8 ]. Huang et al [ 9 ] found that the micropeptide HOXB-AS3 encoded by lncRNA HOXB-AS3 inhibits the growth of colon cancer (CRC), and Polycarpou-Schwarz et al [ 10 ] discovered the micropeptide CASIMO1 (cancer-associated small integral membrane open reading frame 1), which has an oncogenic effect.…”

Section: Introductionmentioning

confidence: 99%

Micropeptide MIAC inhibits the tumor progression by interacting with AQP2 and inhibiting EREG/EGFR signaling in renal cell carcinoma

Liu

Jin

et al. 2022

Mol Cancer

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Background Although, micropeptides encoded by non-coding RNA have been shown to have an important role in a variety of tumors processes, there have been no reports on micropeptide in renal cell carcinoma (RCC). Based on the micropeptide MIAC (micropeptide inhibiting actin cytoskeleton) discovered and named in the previous work, this study screened its tumor spectrum, and explored its mechanism of action and potential diagnosis and treatment value in the occurrence and development of renal carcinoma. Methods The clinical significance of MIAC in RCC was explored by bioinformatics analysis through high-throughput RNA-seq data from 530 patients with kidney renal clear cell carcinoma (KIRC) in the TCGA database, and the detection of clinical samples of 70 cases of kidney cancer. In vitro and in vivo experiments to determine the role of MIAC in renal carcinoma cell growth and metastasis; High-throughput transcriptomics, western blotting, immunoprecipitation, molecular docking, affinity experiments, and Streptavidin pulldown experiments identify MIAC direct binding protein and key regulatory pathways. Results The analysis of 600 renal carcinoma samples from different sources revealed that the expression level of MIAC is significantly decreased, and corelated with the prognosis and clinical stage of tumors in patients with renal carcinoma. Overexpression of MIAC in renal carcinoma cells can significantly inhibit the proliferation and migration ability, promote apoptosis of renal carcinoma cells, and affect the distribution of cells at various stages. After knocking down MIAC, the trend is reversed. In vivo experiments have found that MIAC overexpression inhibit the growth and metastasis of RCC, while the synthetized MIAC peptides can significantly inhibit the occurrence and development of RCC in vitro and in vivo. Further mechanistic studies have demonstrated that MIAC directly bind to AQP2 protein, inhibit EREG/EGFR expression and activate downstream pathways PI3K/AKT and MAPK to achieve anti-tumor effects. Conclusions This study revealed for the first time the tumor suppressor potential of the lncRNA-encoded micropeptide MIAC in RCC, which inhibits the activation of the EREG/EGFR signaling pathway by direct binding to AQP2 protein, thereby inhibiting renal carcinoma progression and metastasis. This result emphasizes that the micropeptide MIAC can provide a new strategy for the diagnosis and treatment of RCC.

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Cancer-related micropeptides encoded by ncRNAs: Promising drug targets and prognostic biomarkers

Cited by 31 publications

References 170 publications

Cancer's Dark Matter: Lighting the Abyss Unveils Universe of New Therapies

Cancer's Dark Matter: Lighting the Abyss Unveils Universe of New Therapies

The DDUP protein encoded by the DNA damage-induced CTBP1-DT lncRNA confers chemoresistance in ovarian cancer

Micropeptide MIAC inhibits the tumor progression by interacting with AQP2 and inhibiting EREG/EGFR signaling in renal cell carcinoma

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