مورد إلكتروني
Hsa_circ_0000098 is a novel therapeutic target that promotes hepatocellular carcinoma development and resistance to doxorubicin
العنوان: | Hsa_circ_0000098 is a novel therapeutic target that promotes hepatocellular carcinoma development and resistance to doxorubicin |
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بيانات النشر: | BioMed Central 2022-09-07 |
تفاصيل مُضافة: | Li, Yi Wu, Anqi Chen, Lin Cai, Aiting Hu, Yuhao Zhou, Zhou Qi, Qianyi Wu, Yixuan Xia, Donglin Dong, Peixin Ju, Shaoqing Wang, Feng |
نوع الوثيقة: | Electronic Resource |
مستخلص: | Background:Circular RNA (circRNA) is crucial to the progression of hepatocellular cancer (HCC). In addition, Mito-chondrial calcium uniporter regulatory factor 1 (MCUR1) is commonly overexpressed in HCC to increase cellular ATP levels. Due to the highly aggressive characteristics of HCC, it is essential to identify new diagnostic biomarkers and therapeutic targets that may facilitate the diagnosis of HCC and the development of effective anti-HCC treatments.Methods:A series of in vitro and in vivo experiments were undertaken to investigate the biological importance and underlying mechanisms of circ_0000098 in HCC.Results:The expression of circ_0000098 was higher in HCC tissues compared to paired adjacent tissues. According to the receiver-operating characteristic curves, circ_0000098 functioned as a potential diagnostic tumor marker in HCC. Our experiments indicated that circ_0000098 served as a key oncogenic circRNA to increase HCC cell prolifera-tion and invasion in vitro and HCC progression in vivo. Furthermore, mechanistic investigation demonstrated that by sequestering miR-383 from the 3′-UTR of MCUR1, circ_0000098 positively regulated MCUR1 expression in HCC cells and finally promoted HCC progression. On the other hand, inhibiting circ_0000098 in HCC cells could diminish doxorubicin (DOX) resistance by decreasing P-glycoprotein (P-gp, MDR1) expression and intracellular ATP levels. Either downregulation of MCUR1 or overexpression of miR-383 improved DOX sensitivity in HCC cells. Subsequently, a short hairpin RNA targeting circ_0000098 (referred to as sh-1) and doxorubicin (DOX) were encapsulated into platelets (PLTs), referred to as DOX/sh-1@PLT. Activated DOX/sh-1@PLT through HCC cells resulted in the creation of platelet-derived particles that were capable of delivering the DOX/sh-1 combination into HCC cells and promoting intracellu-lar DOX accumulation. Furthermore, our in vivo experiments showed that DOX/sh-1@PLT can effectively reduce P-gp expression, prom |
مصطلحات الفهرس: | HCC, circ_0000098, MCUR1, miR-383, P-gp, Platelet, Drug resistance, 490, article |
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الإتاحة: | Open access content. Open access content https://creativecommons.org/licenses/by/4.0 |
ملاحظة: | English |
أرقام أخرى: | YX@ oai:eprints.lib.hokudai.ac.jp:2115/86755 Journal of Experimental & Clinical Cancer Research, 41(1): 267 1400208261 |
المصدر المساهم: | HOKKAIDO UNIV From OAIster®, provided by the OCLC Cooperative. |
رقم الأكسشن: | edsoai.on1400208261 |
قاعدة البيانات: | OAIster |
الوصف غير متاح. |