探討長鏈非編碼核醣核酸於口腔鱗狀細胞癌的致病角色

中山醫學大學機構典藏 CSMUIR > 口腔醫學院 > 牙醫學系暨碩士班 > 博碩士論文 > Item 310902500/19534

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/19534

Title:	探討長鏈非編碼核醣核酸於口腔鱗狀細胞癌的致病角色 To Investigate the Pathogenic Role of Long non-coding RNA (lncRNA) in Oral Squamous Cell Carcinoma Progression
Authors:	呂明怡 Lu, Ming-Yi
Contributors:	中山醫學大學;牙醫學系博士班;余承佳
Keywords:	口腔癌;癌症幹細胞;長鏈非編碼核醣核;HOTAIR;上皮間質轉換 oral cancer;cancer stem cell;lncRNA;HOTAIR;epithelial-mesenchymal transition
Date:	2018
Issue Date:	2019-01-03T08:13:48Z (UTC)
Abstract:	目的：近年來研究顯示長鏈非編碼核醣核酸（long non-coding RNA, lncRNA）可調控多種細胞過程，包括細胞生長、分化、凋亡及腫瘤發生。然而，在口腔鱗狀細胞癌中，長鏈非編碼核醣核酸的功能性角色和其與致癌機轉間交互作用的機制分析依然多屬未知。本篇研究主要探討HOX轉錄本反義核醣核酸（HOX transcript antisense RNA, HOTAIR）對口腔鱗狀細胞癌的影響。材料及方法：我們先檢測HOTAIR在口腔癌細胞及細胞株的表現量去確認其異常表現。再選擇兩株HOTAIR表現較高的口腔癌細胞進一步檢測其癌幹細胞的HOTAIR表現量。利用短夾型RNA去抑制HOTAIR表現後去測量癌幹細胞的醛脫氫?活性(ALDH1)、自我更新能力、爬行力、侵襲力、幹細胞標的物、活體內腫瘤生成能力。並過度表現HOTAIR於癌細胞去驗證其影響力。此外，為了探討HOTAIR影響癌幹性的相關機制，上皮間質轉換過程相關的轉錄因子表現量將由西方墨點法(Western blot)與即時聚合?鏈鎖反應(Real-time polymerase chain reaction)檢測。結果：抑制HOTAIR可顯著地降低口腔癌癌幹細胞之癌幹性、侵襲性、非貼附性生長及異體腫瘤生成能力。反之，口腔癌細胞過度表現HOTAIR可增強其癌幹性及轉移性。Kaplan–Meier存活分析顯示較高的HOTAIR表現與口腔癌患者較差的預後有關。此外，本實驗也證實HOTAIR可藉由上皮間質轉換過程相關的轉錄因子來調控癌幹性。結論：HOTAIR能藉由調節上皮間質轉換來增進癌幹性及轉移性，可作為口腔癌治療的標靶。 Objective: Increasing evidence indicates that long non-coding RNAs (lncRNAs) regulate diverse cellular processes, including cell growth, differentiation, apoptosis, and tumorigenesis. However, the functional roles of lncRNAs and the mechanistic analysis of their interplays with oncogenic pathways in OSCC (oral squamous cell carcinomas) remain largely unknown. This study focused on the effect of HOTAIR (HOX transcript antisense RNA) in OSCC. Materials and Methods: First, we assessed the expression of HOTAIR in various oral cancer cell lines and OSCC tissues to confirm its aberrant expression Subsequently, we selected two oral cancer cells that expressed high HOTAIR for further analysis. Short hairpin RNA was used to downregulate the expression of HOTAIR in oral cancer stem cells (OCSCs) followed by examination of ALDH1 activity , self-renewal, migration, invasion capacities and in vivo tumorigenicity. To unravel the associated mechanism, RT-PCR and Western blot were applied to analyze the expression of epithelial-mesenchymal transition (EMT) markers. Results: Silence of HOTAIR in OCSCs significantly inhibited their cancer stemness, invasiveness, anchorage-independent growth, xenotransplantation tumourigenicity. In contrast, overexpression of HOTAIR in OSCC was found to ehance cancer stemness and metastasis. Kaplan–Meier analysis indicated increased HOTAIR expression correlated with poor survival in OSCC patients. Furthermore, our data suggested that HOTAIR mediated cancer stemness through EMT-associated transcription factors regulation. Conclusion: HOTAIR-mediated cancer stemness is associated with the regulation of EMT. These findings indicate that HOTAIR may be able to act as a therapeutic target in OSCC.
URI:	https://ir.csmu.edu.tw:8080/ir/handle/310902500/19534
Appears in Collections:	[牙醫學系暨碩士班] 博碩士論文

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