Role of LINC01446 in Regulating AK7 Expression and Its Implications for HIF-1α Activity in Hepatocellular Carcinoma
- 주제(키워드) Hepatocellular carcinoma , long non-coding RNA , recurrence , biomarker
- 주제(DDC) 570
- 발행기관 아주대학교 일반대학원
- 지도교수 정재연
- 발행년도 2025
- 학위수여년월 2025. 2
- 학위명 석사
- 학과 및 전공 일반대학원 의생명과학과
- 실제URI http://www.dcollection.net/handler/ajou/000000034648
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Long non-coding RNAs (lncRNAs) have emerged as crucial regulators in hepatocellular carcinoma (HCC) progression and metastasis. This study aims to identify recurrence-associated lncRNAs in HCC and investigate the roles of LINC01446 and its associated gene, AK7, in HCC metastasis and patient prognosis. Through transcriptomic analysis of recurrent versus non-recurrent HCC patient samples, LINC01446 was identified as significantly upregulated in recurrent cases. Integrative analysis using TCGA_LIHC further identified AK7 as a key LINC01446-associated gene, showing strong correlation with LINC01446 expression. In vitro experiments demonstrated that inhibition of LINC01446 and AK7 suppressed cell migration, invasion, and epithelial-Mesenchymal Transition (EMT) in HCC cell lines. Both genes were further shown to play roles in hypoxia response pathways and the regulation of angiogenesis and stemness markers, suggesting their involvement in the tumor microenvironment. In vivo, an orthotopic xenograft mouse model revealed that siLINC01446 and siAK7 treatments significantly reduced tumor burden and intrahepatic metastasis, with IHC analysis confirming decreased EMT and angiogenic marker expression in treated tumors. Survival analysis of HCC patients indicated that high expression of both LINC01446 and AK7 were associated with poor outcomes across overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and progression-free survival (PFS) metrics. These findings suggest that LINC01446 and AK7 contribute to HCC progression through coordinated regulation of metastasis, EMT, and angiogenesis, and may serve as potential biomarkers for HCC prognosis and therapeutic targets.
more목차
Ⅰ. INTRODUCTION 1
Ⅱ. MATERIALS AND METHODS 3
1. Public omics datasets 3
2. Survival analysis 3
3. In vivo models 3
4. Lung hematoxylin and eosin (H&E) and Immunohistochemistry (IHC) 4
5. Patients 5
6. Cell culture and transfection 6
7. RNA extraction and quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) 6
8. RNA-sequencing 7
9. Enrichment analysis 8
10. Wound healing assay 8
11. Transwell assay 8
12. Western blot analysis 9
13. Statical analysis 10
Ⅲ. RESULTS 11
1. Identification of recurrence-associated lncRNAs in HCC and their clinical relevance 11
2. Inhibition of LINC01446 suppresses tumor metastasis in vivo 13
3. Identification of LINC01446-associated genes in HCC cells and their correlation with LINC01446 expression 16
4. Inhibition of LINC01446-associated AK7 suppresses metastasis and invasion ability of HCC cells in vitro 20
5. LINC01446 and AK7 exhibit similar effects on HCC tumor growth and metastasis in vivo, with their overexpression linked to poor patient prognosis 24
Ⅳ. DISCUSSION 28
Ⅴ. REFERENCES 31
국문요약 35
