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Aberrantly Expressed MicroRNAs in Cancer-Associated Fibroblasts and Their Target Oncogenic Signatures in Hepatocellular Carcinoma.

التفاصيل البيبلوغرافية
العنوان: Aberrantly Expressed MicroRNAs in Cancer-Associated Fibroblasts and Their Target Oncogenic Signatures in Hepatocellular Carcinoma.
المؤلفون: Eun JW; Department of Gastroenterology, Ajou University School of Medicine, 164 World cup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea., Ahn HR; Department of Gastroenterology, Ajou University School of Medicine, 164 World cup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea.; Department of Biomedical Sciences, Ajou University Graduate School of Medicine, 164 World cup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea., Baek GO; Department of Gastroenterology, Ajou University School of Medicine, 164 World cup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea., Yoon MG; Department of Gastroenterology, Ajou University School of Medicine, 164 World cup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea., Son JA; Department of Gastroenterology, Ajou University School of Medicine, 164 World cup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea.; Department of Biomedical Sciences, Ajou University Graduate School of Medicine, 164 World cup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea., Weon JH; Department of Gastroenterology, Ajou University School of Medicine, 164 World cup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea.; Department of Biomedical Sciences, Ajou University Graduate School of Medicine, 164 World cup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea., Yoon JH; Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea., Kim HS; Department of Biochemistry, Kosin University College of Medicine, Busan 49267, Republic of Korea., Han JE; Department of Gastroenterology, Ajou University School of Medicine, 164 World cup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea., Kim SS; Department of Gastroenterology, Ajou University School of Medicine, 164 World cup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea., Cheong JY; Department of Gastroenterology, Ajou University School of Medicine, 164 World cup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea., Kim BW; Department of General Surgery, Ajou University School of Medicine, 164 World cup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea., Cho HJ; Department of Gastroenterology, Ajou University School of Medicine, 164 World cup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea.
المصدر: International journal of molecular sciences [Int J Mol Sci] 2023 Feb 21; Vol. 24 (5). Date of Electronic Publication: 2023 Feb 21.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, [2000-
مواضيع طبية MeSH: Carcinoma, Hepatocellular*/metabolism , Liver Neoplasms*/metabolism , Cancer-Associated Fibroblasts*/metabolism , MicroRNAs*/genetics, Humans ; Receptor, Transforming Growth Factor-beta Type I/genetics ; Gene Expression Regulation, Neoplastic ; Cell Proliferation/genetics
مستخلص: Cancer-associated fibroblasts (CAFs) contribute to tumor progression, and microRNAs (miRs) play an important role in regulating the tumor-promoting properties of CAFs. The objectives of this study were to clarify the specific miR expression profile in CAFs of hepatocellular carcinoma (HCC) and identify its target gene signatures. Small-RNA-sequencing data were generated from nine pairs of CAFs and para-cancer fibroblasts isolated from human HCC and para-tumor tissues, respectively. Bioinformatic analyses were performed to identify the HCC-CAF-specific miR expression profile and the target gene signatures of the deregulated miRs in CAFs. Clinical and immunological implications of the target gene signatures were evaluated in The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA_LIHC) database using Cox regression and TIMER analysis. The expressions of hsa-miR-101-3p and hsa-miR-490-3p were significantly downregulated in HCC-CAFs. Their expression in HCC tissue gradually decreased as HCC stage progressed in the clinical staging analysis. Bioinformatic network analysis using miRWalks, miRDB, and miRTarBase databases pointed to TGFBR1 as a common target gene of hsa-miR-101-3p and hsa-miR-490-3p . TGFBR1 expression was negatively correlated with miR-101-3p and miR-490-3p expression in HCC tissues and was also decreased by ectopic miR-101-3p and miR-490-3p expression. HCC patients with TGFBR1 overexpression and downregulated hsa-miR-101-3p and hsa-miR-490-3p demonstrated a significantly poorer prognosis in TCGA_LIHC. TGFBR1 expression was positively correlated with the infiltration of myeloid-derived suppressor cells, regulatory T cells, and M2 macrophages in a TIMER analysis. In conclusion, hsa-miR-101-3p and hsa-miR-490-3p were substantially downregulated miRs in CAFs of HCC, and their common target gene was TGFBR1 . The downregulation of hsa-miR-101-3p and hsa-miR-490-3p , as well as high TGFBR1 expression, was associated with poor clinical outcome in HCC patients. In addition, TGFBR1 expression was correlated with the infiltration of immunosuppressive immune cells.
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معلومات مُعتمدة: 2021R1C1C1009619, 2022R1A2C2092422, 2022R1H1A2093189 Bio & Medical Technology Development Program of the National Research Foundation (NRF); HR21C1003, HR22C173403 Korea Health Technology R&D Project through the Korea Health Industry Development Insti-tute (KHIDI) funded by the Korean government
فهرسة مساهمة: Keywords: TGFBR1; cancer-associated fibroblast; hepatocellular carcinoma; hsa-microRNA-101-3p; hsa-microRNA-490-3p
المشرفين على المادة: EC 2.7.11.30 (Receptor, Transforming Growth Factor-beta Type I)
0 (MicroRNAs)
تواريخ الأحداث: Date Created: 20230311 Date Completed: 20230314 Latest Revision: 20230314
رمز التحديث: 20230314
مُعرف محوري في PubMed: PMC10002073
DOI: 10.3390/ijms24054272
PMID: 36901700
قاعدة البيانات: MEDLINE
الوصف
تدمد:1422-0067
DOI:10.3390/ijms24054272