Downregulation of miR-138 is associated with overexpression of human telomerase reverse transcriptase protein in human anaplastic thyroid carcinoma cell lines.
Alterations of several microRNA (miRNA) have been linked to cancer development and its biology. To search for unique miRNA that might play a role in the development of anaplastic thyroid carcinoma (ATC), we examined the expression of multiple miRNA and their functional effects on target genes in human thyroid carcinoma cell lines. We quantitatively evaluated the expression of multiple miRNA in 10 ATC and five papillary thyroid carcinoma (PTC) cell lines, as well as primary tumors from 11 thyroid carcinoma patients (three ATC and eight PTC), using the stem-loop-mediated reverse transcription real-time polymerase chain reaction method. We also examined the target gene specificity of unique miRNA that showed differences in expression between ATC and PTC cell lines. One miRNA, miR-138, was significantly downregulated in ATC cell lines in comparison with PTC (P < 0.01). Eleven miRNA (including miR-138) potentially targeting the human telomerase reverse transcriptase (hTERT) gene were totally downregulated in both ATC and PTC cell lines in comparison with normal thyroid tissues. A tendency for an inverse correlation between miR-138 and hTERT protein expression was observed in the thyroid cancer cell lines, although this failed to reach significance (r = -0.392, P = 0.148). We demonstrated that overexpression of miR-138 induced a reduction in hTERT protein expression, and confirmed target specificity between miR-138 and the hTERT 3'-untranslated region by luciferase reporter assay. These results suggest that loss of miR-138 expression may partially contribute to the gain of hTERT protein expression in ATC, and that further multiple miRNA targeting hTERT mRNA might be involved in the development of thyroid carcinoma.
Mitomo
Shingo
S
Department of Pathology, School of Medicine, Iwate Medical University, Morioka 020-8505, Japan.
Maesawa
Chihaya
C
Ogasawara
Satoshi
S
Iwaya
Takeshi
T
Shibazaki
Masahiko
M
Yashima-Abo
Akiko
A
Kotani
Koji
K
Oikawa
Hiroki
H
Sakurai
Eiich
E
Izutsu
Naoko
N
Kato
Kuniyuki
K
Komatsu
Hideaki
H
Ikeda
Kenichro
K
Wakabayashi
Go
G
Masuda
Tomoyuki
T
D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism
D035683:MicroRNAs; D012333:RNA, Messenger; C509186:TERT protein, human; D019098:Telomerase