SNHG1 knockdown upregulates miR-376a and downregulates FOXK1/Snail axis to prevent tumor growth and metastasis in HCC

التفاصيل البيبلوغرافية
العنوان: SNHG1 knockdown upregulates miR-376a and downregulates FOXK1/Snail axis to prevent tumor growth and metastasis in HCC
المؤلفون: Qiang He, Lan-Lan Zang, Jing Wang, Aijin Zhou, Fanzhi Meng, Tao Lu, Jinghua Liu
المصدر: Molecular Therapy: Oncolytics, Vol 21, Iss, Pp 264-277 (2021)
Molecular Therapy Oncolytics
بيانات النشر: Elsevier, 2021.
سنة النشر: 2021
مصطلحات موضوعية: 0301 basic medicine, Cancer Research, small nucleolar RNA host gene 1, microRNA-376a, Snail, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Nude mouse, biology.animal, microRNA, medicine, Pharmacology (medical), Viability assay, RC254-282, Gene knockdown, Reporter gene, FOXK1, biology, long non-coding RNA, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, hepatocellular carcinoma, biology.organism_classification, medicine.disease, Long non-coding RNA, digestive system diseases, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cancer research, Molecular Medicine, Original Article
الوصف: Long non-coding RNAs (lncRNAs), microRNAs (miRNAs or miRs), and genes are emerging players in cancer progression. In the present study, we explored the roles and interactions of oncogenic lncRNA small nucleolar RNA host gene 1 (SNHG1), miR-376, forkhead box protein K1 (FOXK1), and Snail in hepatocellular carcinoma (HCC). Expression of SNHG1, miR-376, and FOXK1 in HCC was characterized in clinical HCC tissues of 75 patients with HCC. The interactions between SNHG1 and miR-376 and between miR-376 and FOXK1 were predicted and confirmed by dual-luciferase reporter gene and RNA immunoprecipitation assays. Overexpression and knockdown experiments were performed in HCC cells to examine the effects of the SNHG1/miR-376/FOXK1/Snail axis on viability, apoptosis, invasiveness, and migrating abilities. Their effects on tumor growth and metastasis were validated in nude mouse models. SNHG1 and FOXK1 were upregulated, and miR-376a was downregulated in HCC. SNHG1 knockdown contributed to suppression of HCC cell viability, invasion, and migration properties and promotion of apoptosis. SNHG1 could competitively bind to miR-376a to upregulate its target gene FOXK1, which upregulated Snail. SNHG1 knockdown delayed cancer progression both in vitro and in vivo by upregulating miR-376a and downregulating FOXK1 and Snail. SNHG1 knockdown exerts anti-tumor activity in HCC, suggesting a therapeutic target.
Graphical Abstract
SNHG1 is highly expressed in HCC. SNHG1 competitively binds to miR-376a and inhibits the expression of miR-376a, thereby promoting FOXK1 and Snail expression, leading to reduction of HCC cell proliferative, migrating, and invasive properties, and promotes cell apoptosis and promotion of tumor growth and metastasis in HCC.
اللغة: English
تدمد: 2372-7705
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9ceaa176580ece30ef2c644a3a58759c
http://www.sciencedirect.com/science/article/pii/S2372770521000206
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....9ceaa176580ece30ef2c644a3a58759c
قاعدة البيانات: OpenAIRE