探討新型鋅指蛋白基因家族在結腸直腸癌中扮演的角色

近年來有研究顯示新穎的CCCH type鋅指蛋白家族(zinc finger protein family)是吞噬細胞活化的負向調節因子。而經過廣泛的基因體的研究發現總共存在老鼠體內有58個新穎CCCH type鋅指蛋白基因，人類有55個，但尚未被完整分類與分析其功能。老鼠的58個新穎CCCH type鋅指蛋白家族分為六群。目前已發現老鼠的58個鋅指蛋白家族中，有32個是未知的，其他26個是已知的蛋白，其中有20個蛋白被研究出和RNA代謝相關，包括與mRNA剪接、mRNA的運送、以及mRNA的穩定性和分解相關，另外6個蛋白是牽涉到轉錄(Transcription)、泛素化作用(Ubiquitination)、二磷酸腺苷核糖多聚化(Poly-ADP-Ribosylation)有關。有3個CCCH type鋅指蛋白分別為BC003883、BC019429、以及Zfp36l3被發現只存在於老鼠體內，在人類沒有這三個鋅指蛋白。研究顯示ZC3H12D在癌症中可能扮演腫瘤抑制基因(tumor suppressor gene)；然而，目前人類大部分CCCH type鋅指蛋白的功能或在癌症方面扮演的角色是尚未深入了解的。因此，我們想探討新穎CCCH type鋅指蛋白家族和結腸直腸癌的相關性。本實驗中我們收集臨床結腸直腸癌組織檢體利用qRT –PCR方法篩選CCCH type鋅指蛋白mRNA表現量，發現ZC3HAV1L在結腸直腸癌的組織中比正常組織有相對高的表現量。接著進一步探討ZC3HAV1L對於結腸直腸癌細胞的影響，利用慢病毒(lentivirus)方法建立ZC3HAV1L knockdown stable cell line以及過度表現ZC3HAV1L於結腸直腸癌細胞，我們發現高度表現ZC3HAV1L會增加結腸直腸癌細胞增生及cell migration的情形；而抑制ZC3HAV1L的表現會減少結腸直腸癌細胞增生及cell migration的情形。由此得知，ZC3HAV1L可能在結腸直腸癌中扮演促進細胞增生的角色。

關鍵字

新型鋅指蛋白

並列摘要

Previous studies have identified a novel CCCH zinc finger protein family as negative regulators of macrophage activation. And recent reports have indicated totally 58 CCCH zinc finger genes in mouse and 55 in human were identified . Phylogenetic analysis have revealed that the mouse CCCH family was divided into 6 groups. Out of the 58 mouse CCCH zinc finger proteins, 32 proteins were totally unknown. Among the other 26 known proteins, 20 proteins have been reported to be involved in RNA metabolisms including pre-mRNA splicing, mRNA transportation, subcellular localization, and stability/degradation.The other six CCCH proteins were involved in transcription, ubiquitination, and poly ADP-ribosylation. Three CCCH genes BC003883, BC019429 and Zfp36l3 were only found in murine genome, but not human. Besides, previous reports have shown ZC3H12D might play a critical role regulating cancer cells growth and/or survival. However, functions of many CCCH type zinc finger proteins in cancers are unknown. In this study, we have screened the expression profile of CCCH zinc finger gene family in human colorectal cancer tissues, and found the ZC3HAV1L gene was significant up-regulation. To investigate the functions of ZC3HAV1L in colorectal cancer cells, we knockdowned or overexpressed ZC3HAV1L gene by a lentivirus-mediated gene delivery system. We found overexpression of ZC3HAV1L increased colorectal cancer cell viability, colony formation, and migration. And knockdown of ZC3HAV1L in SW620 cells decreased cell viability, colony formation, and migration. These results suggest that ZC3HAV1L may play a role in colorectal cancer proliferation.

並列關鍵字

novel zinc finger gene

參考文獻

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探討新型鋅指蛋白基因家族在結腸直腸癌中扮演的角色

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