肝癌為遍布世界各地的疾病，特別在亞洲地區，肝癌更屬於好發性且預後情況較差的癌症。目前已知代謝異常是肝癌形成的危險因子之一。長鏈脂肪酸延長酶 6 (elongation of long chain fatty acids family member 6, ELOVL6) 為一種脂肪酸延長酶，專一作用在延長 12、14 及 16 碳的飽和脂肪酸與單元不飽和脂肪酸。因此，ELOVL6 在脂質合成活躍的器官或組織，例如肝臟和脂肪中有較高的表現量。有研究指出，參與脂質合成的酵素在肝癌中較為活化，並且 ELOVL6 的表現也高於正常組織。在本研究中，主要探討 ELOVL6 對於肝癌細胞生長的影響。我們發現利用腺病毒攜帶核醣核酸干擾因子抑制 ELOVL6 的表現，可抑制小鼠肝癌細胞的增生，並且這種抑制機制主要為使細胞週期停滯在 G1 期。當 ELOVL6 的表現量降低後，發現細胞內的脂質代謝作用，包含脂質的堆積與氧化現象有增加的情形，此脂質代謝的改變可能由細胞內 16 碳脂肪酸的比例增加造成。由小鼠皮下肝腫瘤模式中，我們發現抑制 ELOVL6 的表現可以抑制腫瘤的生長。綜合以上結果，我們在細胞與動物實驗中抑制 ELOVL6 的表現，皆可抑制肝癌細胞的生長。因此，利用腺病毒攜帶 ELOVL6 的核醣核酸干擾因子在肝癌的治療上，可作為一個具有潛力的方法。

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide, particularly in Asia. The prognosis of HCC is poor. Metabolic dysregulation is one of the risk factors for the development of HCC. Elongation of long chain fatty acids family member 6 (ELOVL6), also known as LCE and FACE, is a long chain fatty acid elongase that specifically catalyzes the elongation of saturated and monounsaturated fatty acids with 12, 14, and 16 carbons. ELOVL6 is highly expressed in the liver and adipose tissue where lipogenesis is active. Previous studies have shown that lipogenic enzymes, including ELOVL6, were activated in HCC. In this study, we aimed to investigate the effects of ELOVL6 on the growth of HCC. We found that knockdown of ELOVL6 expression in ML-1 murine hepatoma cells induced morphological changes and growth inhibition due to cell cycle arrest at the G1 phase. In addition, knockdown of ELOVL6 in ML-1 cells increased lipid accumulation and β-oxidation, suggesting that downregulation of ELOVL6 results in cell cycle arrest through the alteration of lipid metabolism. Furthermore, tumor growth was suppressed by adenovirus-mediated ELOVL6 gene silencing through RNA interference in a subcutaneous ML-1 tumor model. Altogether, our in vitro and in vivo results suggest that adenovirus-mediated ELOVL6 gene silencing may have therapeutic potential for the treatment of liver cancer.

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