MicroRNA-1322 regulates ECRG2 allele specifically and acts as a potential biomarker in patients with esophageal squamous cell carcinoma.
A short tandem repeat (STR) polymorphism in the 3'UTR region of esophageal cancer-related gene 2 (ECRG2, also known as SPINK7) has been widely reported to be associated with the incidence and the prognosis of esophageal squamous cell carcinoma (ESCC). This study explores how the microRNA binding to the STR region affects ECRG2 expression in ESCC. Dual-luciferase reporter assays were used to verify the effects of the four microRNAs (miR-580, miR-1182, miR-1272, and miR-1322) predicted to bind the STR region of the ECRG2 3' untranslated region (UTR). The expression of identified effective microRNA was then analyzed in 44 paired ESCC and adjacent normal tissues and 402 case-controlled serum samples (divided into a discovery group and an independent validation group) by real-time RT-PCR assay. We found that only miR-1322 could significantly down-regulate the ECRG2 with TCA3 allele (P < 0.01), but it could not down-regulate the ECRG2 with TCA4 allele significantly (P > 0.05). MiR-1322 was also expressed significantly higher in ESCC tissue and serum samples than in controls (both P < 0.01). Additionally, serum levels of miR-1322 yielded an under receiver operating characteristic (ROC) curve area of 0.847 (95% CI, 0.795-0.890) for discriminating ESCCs from healthy controls in the discovery group and a similar result was obtained in the validation group (under ROC area is 0.845; 95%CI, 0.780-0.897). We conclude that miR-1322 can regulate ECRG2 in an allele-specific manner and that serum levels of miR-1322 can serve as a potential diagnostic biomarker for patients with ESCC.
State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Tengfei
T
Zhang
Dan
D
Zhao
Qiming
Q
Wang
Xiying
X
Yu
Yaling
Y
Cui
Liping
L
Guo
Shih Hsin
SH
Lu
D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D020029:Base Pairing; D001483:Base Sequence; D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D023061:Gene Order; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D018895:Microsatellite Repeats; D008875:Middle Aged; D009690:Nucleic Acid Conformation; D011110:Polymorphism, Genetic; D053491:Proteinase Inhibitory Proteins, Secretory / Q000737:chemistry / Q000235:genetics*; D034622:RNA Interference; D000074162:Serine Peptidase Inhibitors, Kazal Type
D020413:3' Untranslated Regions; D014408:Biomarkers, Tumor; C583581:MIRN1322 microRNA, human; C577667:MIRN580 microRNA, human; D035683:MicroRNAs; D053491:Proteinase Inhibitory Proteins, Secretory; C473799:SPINK7 protein, human; D000074162:Serine Peptidase Inhibitors, Kazal Type