Long non-coding RNA 91H contributes to the occurrence and progression of esophageal squamous cell carcinoma by inhibiting IGF2 expression.
Long non-coding RNAs (lncRNAs) have been recently recognized as a major class of regulators in mammalian systems. 91H, a novel long noncoding antisense transcripts located on the position of the H19/IGF2 locus has been suggested to play a potential tumor-suppressor role in tumor development. However, little study has proved the mechanism in esophageal squamous cell carcinoma (ESCC). We carried out this study to explore the role of lncRNA 91H in the regulation of H19 imprinting control regions (ICR) and IGF2 expression and the association between 91H and ESCC progression. The cell line TE-1, Eca-109, and 232 ESCC patients' matched sets of paraffin-embedded adjacent normal and tumor samples were obtained in this study. The results showed that 91H expression was significantly lower in patients with higher depth of invasion, neoplastic grading and TNM which usually leads to the overexpression of IGF2 in tumor progression. The expression of 91H usually decreased in TE-1 and Eca-109 when treated with demethylation agent. Further analysis revealed that, in 91H knockdown cell lines, IGF2 expression was also significantly higher than negative controls. Therefore, the results demonstrated that the lncRNA 91H was associated with H19 ICR methylation and inhibited IGF2 expression of ESCC patients which may optimize the mechanism of IGF2 regulation in tumor development. Patients with higher depth of invasion, neoplastic grading and TNM usually demonstrated lower 91H expression potentially represent a novel clinically relevant event to identify individuals at increased risk for the occurrence, progression and prognosis of ESCC.
Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
Tianyi
T
Gao
Bangshun
B
He
Yuqin
Y
Pan
Yeqiong
Y
Xu
Rui
R
Li
Qiwen
Q
Deng
Huilin
H
Sun
Shukui
S
Wang
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000556:secondary*; D019175:DNA Methylation; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005455:Fluorescent Antibody Technique; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D018392:Genomic Imprinting; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D016372:RNA, Antisense / Q000494:pharmacology*; D062085:RNA, Long Noncoding / Q000037:antagonists & inhibitors* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
C094335:H19 long non-coding RNA; D016372:RNA, Antisense; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; C000621689:long non-coding RNA 91H, human; D007335:Insulin-Like Growth Factor II
91H; ESCC; H19 ICR; IGF2; expression; lncRNA; methylation