Identification of a novel gene HEPT3 that is overexpressed in human hepatocellular carcinoma and may function through its noncoding RNA.
Genetic alterations have been defined as the hallmark of cancers as they are responsible for the differences between normal and malignant phenotypes. A widely accepted approach to study genetic instability is to identify cancer-related genes, in particular, the two major groups of growth regulatory genes - oncogenes and tumour suppressor genes. Using the technique of suppression subtractive hybridisation, we identified a novel gene transcript, designated as HEPT3. RT-PCR demonstrated that HEPT3 was overexpressed in 87% (20/23) of HCC patients and in 4/5 HCC cell lines tested. Sequence analyses performed on the full-length cDNA revealed that HEPT3 is an intronless gene mapped to human chromosome 6q13-14. The gene transcript lacks an extensive open reading frame and contains an Alu sequence near the 5' terminus, indicating that HEPT3 encodes a noncoding RNA. Antisense studies on the HCC cell line HepG2 showed that, when HEPT3 expression level was reduced, cell proliferation rate was inhibited by approximately 5-fold and cell colony formation was reduced by at least 50%. Our data suggest that the novel gene HEPT3 may function through its noncoding RNA and its overexpression may play a role in hepatocarcinogenesis.
Moh
Mei Chung
MC
Laboratory of Hepato-Oncogenetics, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597.
Lee
Lay Hoon
LH
Yang
Xiaodong
X
Shen
Shali
S
D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002896:Chromosomes, Human, Pair 6; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009693:Nucleic Acid Hybridization; D016376:Oligonucleotides, Antisense / Q000737:chemistry; D012334:RNA, Neoplasm / Q000378:metabolism; D022661:RNA, Untranslated; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D018076:DNA, Complementary; C523391:HEPT3 protein, human; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense; D012334:RNA, Neoplasm; D022661:RNA, Untranslated