Methods, Год журнала: 2023, Номер 220, С. 38 - 54
Опубликована: Окт. 25, 2023
Язык: Английский
Molecular Cancer, Год журнала: 2022, Номер 21(1)
Опубликована: Сен. 19, 2022
Abstract Background Although, micropeptides encoded by non-coding RNA have been shown to an important role in a variety of tumors processes, there no reports on micropeptide renal cell carcinoma (RCC). Based the MIAC (micropeptide inhibiting actin cytoskeleton) discovered and named previous work, this study screened its tumor spectrum, explored mechanism action potential diagnosis treatment value occurrence development carcinoma. Methods The clinical significance RCC was bioinformatics analysis through high-throughput RNA-seq data from 530 patients with kidney clear (KIRC) TCGA database, detection samples 70 cases cancer. In vitro vivo experiments determine growth metastasis; High-throughput transcriptomics, western blotting, immunoprecipitation, molecular docking, affinity experiments, Streptavidin pulldown identify direct binding protein key regulatory pathways. Results 600 different sources revealed that expression level is significantly decreased, corelated prognosis stage Overexpression cells can inhibit proliferation migration ability, promote apoptosis cells, affect distribution at various stages. After knocking down MIAC, trend reversed. found overexpression metastasis RCC, while synthetized peptides vivo. Further mechanistic studies demonstrated directly bind AQP2 protein, EREG/EGFR activate downstream pathways PI3K/AKT MAPK achieve anti-tumor effects. Conclusions This for first time suppressor lncRNA-encoded which inhibits activation signaling pathway thereby progression metastasis. result emphasizes provide new strategy RCC.
Язык: Английский
Процитировано
41
Cancer Research, Год журнала: 2023, Номер 83(15), С. 2496 - 2512
Опубликована: Июнь 16, 2023
Long noncoding RNAs (lncRNA) regulate a number of aspects cancer biology. Recent research has shown that lncRNAs can encode micropeptides mediate their functions in tumors. Here, we revealed the liver-specific putative lncRNA, AC115619, is expressed at low levels hepatocellular carcinoma (HCC) and encodes micropeptide, designated as AC115619-22aa. AC115619 played crucial role regulation tumor progression was prognostic indicator HCC. The encoded micropeptide AC115619-22aa inhibited HCC by binding to WTAP impeding assembly N6-methyladenosine (m6A) methyltransferase complex, which regulates expression tumor-associated genes, such SOCS2 ATG14. cotranscribed with adjacent upstream coding gene APOB, hypoxia induced transcriptional repression both APOB controlling HIF1A/HDAC3 HNF4A signaling. In animal patient-derived models, reduced global m6A suppressed growth. conclusion, this study establishes its potential markers therapeutic targets for patients HCC.A lncRNA impedes formation methylation complex lower reduce growth carcinoma.
Язык: Английский
Процитировано
31
Cancers, Год журнала: 2023, Номер 15(13), С. 3506 - 3506
Опубликована: Июль 5, 2023
Cancer represents a significant and persistent global health burden, with its impact underscored by prevalence devastating consequences. Whereas numerous oncogenes could contribute to cancer development, group of transcription factors (TFs) are overactive in the majority tumors. Targeting these TFs may also combat downstream activated TFs, making them attractive potential targets for effective antitumor therapeutic strategy. One such TF is yin yang 1 (YY1), which plays crucial roles development progression various In preclinical studies, YY1 inhibition has shown efficacy inhibiting tumor growth, promoting apoptosis, sensitizing cells chemotherapy. Recent studies have revealed combining immunotherapy enhanced effects. However, clinical translation YY1-targeted therapy still faces challenges drug specificity delivery. This review provides an overview biology, role progression, as well strategies explored therapy, focus on their implications, including those using small molecule inhibitors, RNA interference, gene editing techniques. Finally, we discuss current limitations targeting need further research this area.
Язык: Английский
Процитировано
30
Molecular Therapy — Nucleic Acids, Год журнала: 2023, Номер 33, С. 774 - 793
Опубликована: Июль 16, 2023
Long non-coding RNAs (lncRNAs) are a class of RNA transcripts more than 200 nucleotides in length that play crucial roles cancer development and progression. With the rapid high-throughput sequencing technology, considerable number lncRNAs have been identified as novel biomarkers for predicting prognosis patients and/or therapeutic targets therapy. In recent years, increasing evidence has shown biological functions regulatory mechanisms closely associated with their subcellular localization. More importantly, based on important regulating progression (e.g., growth, resistance, metastasis) specific ability nucleic acids siRNA, mRNA, DNA) to regulate expression any target genes, much effort exerted recently develop nanoparticle (NP)-based acid delivery systems
Язык: Английский
Процитировано
23
Biochemical Pharmacology, Год журнала: 2024, Номер 224, С. 116218 - 116218
Опубликована: Апрель 21, 2024
Язык: Английский
Процитировано
11
Cancer Letters, Год журнала: 2024, Номер 588, С. 216794 - 216794
Опубликована: Март 6, 2024
Язык: Английский
Процитировано
8
Cancer Cell International, Год журнала: 2024, Номер 24(1)
Опубликована: Апрель 15, 2024
Abstract Some noncoding RNAs (ncRNAs) carry open reading frames (ORFs) that can be translated into micropeptides, although have been previously assumed to constitute a class of RNA transcripts without coding capacity. Furthermore, recent studies revealed ncRNA-derived micropeptides exhibit regulatory functions in the development many tumours. Although some these inhibit tumour growth, others promote it. Understanding role ncRNA-encoded cancer poses new challenges for research, but also offers promising prospects therapy. In this review, we summarize types ncRNAs encode highlighting technical developments made it easier research such as ribosome analysis, mass spectrometry, bioinformatics methods, and CRISPR/Cas9. based on distribution different subcellular locations, explain biological human cancers discuss their underestimated potential diagnostic biomarkers anticancer therapeutic targets clinical applications, information may contribute discovery micropeptide-based tools early diagnosis drug development.
Язык: Английский
Процитировано
8
Cancer Letters, Год журнала: 2023, Номер 578, С. 216442 - 216442
Опубликована: Окт. 16, 2023
Язык: Английский
Процитировано
20
Cell Death and Disease, Год журнала: 2023, Номер 14(8)
Опубликована: Авг. 26, 2023
Sustained activation of DNA damage response (DDR) signaling has been demonstrated to play vital role in chemotherapy failure cancer. However, the mechanism underlying DDR sustaining cancer cells remains unclear. In current study, we found that expression DDUP microprotein, encoded by CTBP1-DT lncRNA, drastically increased cisplatin-resistant ovarian and was inversely correlated cisplatin-based therapy response. Using a patient-derived human cell model, observed damage-induced foci sustained RAD18/RAD51C RAD18/PCNA complexes at sites damage, consequently resulting cisplatin resistance through dual RAD51C-mediated homologous recombination (HR) proliferating nuclear antigen (PCNA)-mediated post-replication repair (PRR) mechanisms. Notably, treatment with an ATR inhibitor disrupted DDUP/RAD18 interaction abolished effect on prolonged signaling, which resulted hypersensitivity vivo. Altogether, our study provides insights into DDUP-mediated aberrant describes potential novel therapeutic approach for management platinum-resistant
Язык: Английский
Процитировано
19
Expert Opinion on Drug Discovery, Год журнала: 2023, Номер 18(9), С. 1011 - 1029
Опубликована: Июль 19, 2023
Introduction lncRNAs are major players in regulatory networks orchestrating multiple cellular functions, such as 3D chromosomal interactions, epigenetic modifications, gene expression and others. Due to progress the development of nucleic acid-based therapeutics, potentially represent easily accessible therapeutic targets.Areas covered Currently, significant efforts directed at studies that can tap enormous potential lncRNAs. This review describes recent developments this field, particularly focusing on clinical applications.Expert opinion Extensive druggable target range lncRNA combined with high specificity accelerated process therapeutics open new prospects for treatment areas extreme unmet medical need, genetic diseases, aggressive cancers, protein deficiencies, subsets common diseases caused by known mutations. Although currently wide acceptance lncRNA-targeting is impeded need parenteral or direct-to-CNS administration, less invasive techniques orally available/BBB-penetrant showing early successes. Recently, mRNA-based COVID-19 vaccines have demonstrated safety all aspects technology, including chemical modifications acids nanoparticle delivery. These trends position drugs future drug development, especially area personalized medicine.
Язык: Английский
Процитировано
15