Aberrant Splicing of Hugl-1 Is Associated with Hepatocellular Carcinoma Progression

	Aberrant Splicing of Hugl-1 Is Associated with Hepatocellular Carcinoma Progression
	Lu, XF; Feng, XJ; Man, XB; Yang, G; Tang, L; Du, D; Zhang, F; Yuan, HX; Huang, Q; Zhang, Z
刊名	CLINICAL CANCER RESEARCH
	2009
卷号	15 期号:10 页码:3287-3296
通讯作者	Chen, ZJ (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, 320 Yueyang Rd, Shanghai 200031, Peoples R China.,zichen@sibs.ac.cn
英文摘要	Purpose: Lethal giant larvae functions as a cell polarity regulator and a tumor suppressor in Drosophila. Its evolutionary conservation implies a tumor suppressor role for its human homologue, Hugl-1. The aims of this study were to characterize Hugl-1 and to determine the clinical significance of Hugl-1 alterations in hepatocellular carcinoma (HCC). Experimental Design: Sequence alterations of Hugl-l from 80 HCC specimens and 5 HCC cell lines were characterized by reverse transcription-PCR and sequence analysis. Western blot was used for determining Hugl-1 expression. The biological activities of Hugl-1 and its aberrant variants were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-di-phenyltetrazolium bromide assay, wound healing assay, Boyden chamber assay, and tumorigenicity assay. Results: In 32.5% (26 of 80) of the specimens and 20.0% (one of five) of HCC cell lines, 23 unique aberrant Hugl-1 transcripts were identified, most of which resulted from skipping part of and/or entire exon or insertion of intron sequences. The majority of these aberrant Hugl-1 transcripts encoded truncated proteins lacking one or more conserved WD-40 repeat motifs. Two truncated Hugl-1 proteins were found exclusively in HCC tissues. Aberrant Hugl-1 transcripts (78.3%, 20 of 23) had a short "direct repeat" sequence flanking their deleted regions. The abnormal Hugl-1 was significantly correlated with poor differentiation and large tumor size of HCC. Overexpression of two representative HCC-derived aberrant Hugl-1 variants promoted HCC cell migration, invasion, and tumorigenicity in nude mice. Conclusions: We provide the first evidence that Hugl-1 mRNA is frequently mutated by aberrant splicing exclusively in HCC, which may be involved in HCC progression.
学科主题	Oncology
类目[WOS]	Oncology
关键词[WOS]	CELL POLARITY ; MESSENGER-RNA ; CYTOSKELETAL PROTEIN ; HUMAN HOMOLOG ; GIANT LARVAE ; DROSOPHILA ; CANCER ; EXPRESSION ; MUTATIONS ; TUMORS
收录类别	SCI
语种	英语
WOS记录号	WOS:000266282600007
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1252]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Lu, XF,Feng, XJ,Man, XB,et al. Aberrant Splicing of Hugl-1 Is Associated with Hepatocellular Carcinoma Progression[J]. CLINICAL CANCER RESEARCH,2009,15(10):3287-3296.
APA	Lu, XF.,Feng, XJ.,Man, XB.,Yang, G.,Tang, L.,...&Chen, ZJ.(2009).Aberrant Splicing of Hugl-1 Is Associated with Hepatocellular Carcinoma Progression.CLINICAL CANCER RESEARCH,15(10),3287-3296.
MLA	Lu, XF,et al."Aberrant Splicing of Hugl-1 Is Associated with Hepatocellular Carcinoma Progression".CLINICAL CANCER RESEARCH 15.10(2009):3287-3296.