Telomeric 3' overhangs in chronic HBV-related hepatitis and hepatocellular carcinoma.
Telomeric 3' overhang is a key component of telomere structure, but little is known about its role in hepatocarcinogenesis. We examined the 3' overhang and telomere length, mRNA levels of hTERT, POT1, TRF1 and cytokeratin 19 (CK19) in 41 hepatitis B virus (HBV)-related hepatocellular carcinomas (HCCs) and adjacent non-HCCs of B viral chronic hepatitis/cirrhosis. 3' overhang length was positively correlated with telomere length (p < 0.001). In non-HCCs, the 3' overhang shortened with increasing age (p = 0.043). Twenty-six HCCs had shorter and 15 HCCs had longer 3' overhangs than the adjacent non-HCCs. The mRNA levels of hTERT, POT1 and TRF1 were upregulated in HCCs than in non-HCCs. HCCs with lengthened 3' overhangs expressed higher hTERT mRNA levels than those with shortened 3' overhangs, when compared to 3' overhangs in non-HCCs (p = 0.044). POT1 and TRF1 showed no significant difference according to the 3' overhangs. HCCs with long 3' overhangs had higher mitosis (p = 0.046) and more frequent multipolar mitosis compared to those with short 3' overhangs (p = 0.034). HCCs with high cytokeratin 19 mRNA levels, a marker for hepatic progenitor cells, had longer 3' overhangs than HCCs with low cytokeratin 19 mRNA levels (p= 0.019). In conclusion, the 3' overhang erosion might be closely related to the number of cell divisions in telomerase-negative hepatocytes of chronic hepatitis/cirrhosis. In telomerase-positive HCCs, an altered 3' overhang are involved in HBV-related hepatocarcinogenesis and hTERT might be involved in regulation of 3' overhang.
Lee
Jae-Eun
JE
Department of Pathology, Center for Chronic Metabolic Disease, Institute of Gastroenterology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemoon-gu, Seoul, 120-752, Korea.
Oh
Bong-Kyeong
BK
Cancer Metastasis Research Center, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemoon-gu, Seoul, 120-752, Korea.
Choi
Jinsub
J
Department of General Surgery, Yonsei University College of Medicine, Seoul, Korea.
Park
Young Nyun
YN
Department of Pathology, Center for Chronic Metabolic Disease, Institute of Gastroenterology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemoon-gu, Seoul, 120-752, Korea.
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics* / Q000821:virology; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications*; D006801:Humans; D053539:Keratin-19 / Q000032:analysis; D008103:Liver Cirrhosis / Q000235:genetics; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D000089804:Shelterin Complex; D019098:Telomerase / Q000032:analysis* / Q000235:genetics; D016615:Telomere; D034501:Telomere-Binding Proteins / Q000032:analysis; D035321:Telomeric Repeat Binding Protein 1 / Q000032:analysis
D053539:Keratin-19; C440849:POT1 protein, human; D012333:RNA, Messenger; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D035321:Telomeric Repeat Binding Protein 1; C509186:TERT protein, human; D019098:Telomerase