دورية أكاديمية
Developing Folate-Conjugated miR-34a Therapeutic for Prostate Cancer: Challenges and Promises
| العنوان: | Developing Folate-Conjugated miR-34a Therapeutic for Prostate Cancer: Challenges and Promises |
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| المؤلفون: | Wen (Jess) Li, Yunfei Wang, Xiaozhuo Liu, Shan Wu, Moyi Wang, Steven G. Turowski, Joseph A. Spernyak, Amanda Tracz, Ahmed M. Abdelaal, Kasireddy Sudarshan, Igor Puzanov, Gurkamal Chatta, Andrea L. Kasinski, Dean G. Tang |
| المصدر: | International Journal of Molecular Sciences, Vol 25, Iss 4, p 2123 (2024) |
| بيانات النشر: | MDPI AG, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | microRNA-34a, microRNA, prostate cancer, folate receptor, PSMA, miRNA therapeutics, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | Prostate cancer (PCa) remains a common cancer with high mortality in men due to its heterogeneity and the emergence of drug resistance. A critical factor contributing to its lethality is the presence of prostate cancer stem cells (PCSCs), which can self-renew, long-term propagate tumors, and mediate treatment resistance. MicroRNA-34a (miR-34a) has shown promise as an anti-PCSC therapeutic by targeting critical molecules involved in cancer stem cell (CSC) survival and functions. Despite extensive efforts, the development of miR-34a therapeutics still faces challenges, including non-specific delivery and delivery-associated toxicity. One emerging delivery approach is ligand-mediated conjugation, aiming to achieve specific delivery of miR-34a to cancer cells, thereby enhancing efficacy while minimizing toxicity. Folate-conjugated miR-34a (folate–miR-34a) has demonstrated promising anti-tumor efficacy in breast and lung cancers by targeting folate receptor α (FOLR1). Here, we first show that miR-34a, a TP53 transcriptional target, is reduced in PCa that harbors TP53 loss or mutations and that miR-34a mimic, when transfected into PCa cells, downregulated multiple miR-34a targets and inhibited cell growth. When exploring the therapeutic potential of folate–miR-34a, we found that folate–miR-34a exhibited impressive inhibitory effects on breast, ovarian, and cervical cancer cells but showed minimal effects on and targeted delivery to PCa cells due to a lack of appreciable expression of FOLR1 in PCa cells. Folate–miR-34a also did not display any apparent effect on PCa cells expressing prostate-specific membrane antigen (PMSA) despite the reported folate’s binding capability to PSMA. These results highlight challenges in the specific delivery of folate–miR-34a to PCa due to a lack of target (receptor) expression. Our study offers novel insights into the challenges and promises within the field and casts light on the development of ligand-conjugated miR-34a therapeutics for PCa. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1422-0067 1661-6596 |
| Relation: | https://www.mdpi.com/1422-0067/25/4/2123; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067 |
| DOI: | 10.3390/ijms25042123 |
| URL الوصول: | https://doaj.org/article/e53665e2fdbf4db98c8a6545b64a0204 |
| رقم الأكسشن: | edsdoj.53665e2fdbf4db98c8a6545b64a0204 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14220067 16616596 |
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| DOI: | 10.3390/ijms25042123 |