Academic Journal
The microRNA target site profile is a novel biomarker in the immunotherapy response
| العنوان: | The microRNA target site profile is a novel biomarker in the immunotherapy response |
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| المؤلفون: | Yulong Bai, Yujia Li, Yidi Qin, Xinshuo Yang, George C. Tseng, Soyeon Kim, Hyun Jung Park |
| المصدر: | Frontiers in Oncology, Vol 13 (2023) |
| بيانات النشر: | Frontiers Media S.A. |
| سنة النشر: | 2023 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | RNA-level regulation, microRNA binding mechanism, tumor initiation, cancer biology, biomarker, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | MicroRNAs (miRNAs) bind on the 3′ untranslated region (3′UTR) of messenger RNAs (mRNAs) and regulate mRNA expression in physiological and pathological conditions, including cancer. Thus, studies have identified miRNAs as potential biomarkers by correlating the miRNA expression with the expression of important mRNAs and/or clinical outcomes in cancers. However, tumors undergo pervasive 3′UTR shortening/lengthening events through alternative polyadenylation (APA), which varies the number of miRNA target sites in mRNA, raising the number of miRNA target sites (numTS) as another important regulatory axis of the miRNA binding effects. In this study, we developed the first statistical method, BIOMATA-APA, to identify predictive miRNAs based on numTS features. Running BIOMATA-APA on The Cancer Genome Atlas (TCGA) and independent cohort data both with immunotherapy and no immunotherapy, we demonstrated for the first time that the numTS feature 1) distinguishes different cancer types, 2) predicts tumor proliferation and immune infiltration status, 3) explains more variation in the proportion of tumor-infiltrating immune cells, 4) predicts response to immune checkpoint blockade (ICB) therapy, and 5) adds prognostic power beyond clinical and miRNA expression. To the best of our knowledge, this is the first pan-cancer study to systematically demonstrate numTS as a novel type of biomarker representing the miRNA binding effects underlying tumorigenesis and pave the way to incorporate miRNA target sites for miRNA biomarker identification. Another advantage of examining the miRNA binding effect using numTS is that it requires only RNA-Seq data, not miRNAs, thus resulting in high power in the miRNA biomarker identification. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2234-943X |
| Relation: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1225221/full; https://doaj.org/toc/2234-943X; https://doaj.org/article/b5c51a3cfd1d48ec839d95a908b84cc7 |
| DOI: | 10.3389/fonc.2023.1225221 |
| الاتاحة: | https://doi.org/10.3389/fonc.2023.1225221 https://doaj.org/article/b5c51a3cfd1d48ec839d95a908b84cc7 |
| رقم الانضمام: | edsbas.2AA71495 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 2234943X |
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| DOI: | 10.3389/fonc.2023.1225221 |