TY - JOUR
T1 - MicroRNA-196a is a potential marker of progression during Barrett's metaplasia-dysplasia-invasive adenocarcinoma sequence in esophagus
AU - Maru, Dipen M.
AU - Singh, Rajesh R.
AU - Hannah, Christina
AU - Albarracin, Constance T.
AU - Li, Yong X.
AU - Abraham, Ronald
AU - Romans, Angela M.
AU - Yao, Hui
AU - Luthra, Madan G.
AU - Anandasabapathy, Sharmila
AU - Swisher, Stephen G.
AU - Hofstetter, Wayne L.
AU - Rashid, Asif
AU - Luthra, Rajyalakshmi
N1 - Funding Information:
Supported by the University of Texas M.D. Anderson Cancer Center, Division of Pathology and Laboratory Medicine (fellow research funding to C.H.).
PY - 2009/5
Y1 - 2009/5
N2 - Barrett's esophagus (BE)/Barrett's metaplasia (BM) is a recognized precursor of esophageal adenocarcinoma (EA) with an intermediary stage of dysplasia. The low yield and high cost of endoscopic screening of patients with BE underscores the need for novel biomarkers, such as microRNA (miRNA), which have emerged as important players in neoplastic progression for risk assessment of developing dysplasia/adenocarcinoma. Recently, we reported highly elevated levels of miRNA-196a (miR-196a) in EA and demonstrated its growth-promoting and anti-apoptotic functions. Here, we evaluated miR-196a as a marker of BE progression to low-grade dysplasia, high-grade dysplasia, and EA using microdissected paraffin-embedded tissues from 11 patients. Higher levels of miR-196a were observed in EA, BE, and dysplastic lesions compared with normal squamous mucosa, and in high-grade dysplasia compared with BE and lowgrade dysplasia. Using frozen tumor tissues from 10 additional patients who had advanced EA, we evaluated the correlation of miR-196a with its in silicopredicted targets, keratin 5 (KRT5), small prolinerich protein 2C (SPRR2C), and S100 calcium-binding protein A9 (S100A9), which are down-regulated during BE progression. MiR-196a levels inversely correlated with the predicted target mRNA levels in EA. We confirmed that miR-196a specifically targets KRT5, SPRR2C, and S100A9 3′ UTRs using miR-196a-mimic and luciferase reporter-based assays. In conclusion, this study identified miR-196a as a potential marker of progression of BE and KRT5, SPRR2C, and S100A9 as its targets.
AB - Barrett's esophagus (BE)/Barrett's metaplasia (BM) is a recognized precursor of esophageal adenocarcinoma (EA) with an intermediary stage of dysplasia. The low yield and high cost of endoscopic screening of patients with BE underscores the need for novel biomarkers, such as microRNA (miRNA), which have emerged as important players in neoplastic progression for risk assessment of developing dysplasia/adenocarcinoma. Recently, we reported highly elevated levels of miRNA-196a (miR-196a) in EA and demonstrated its growth-promoting and anti-apoptotic functions. Here, we evaluated miR-196a as a marker of BE progression to low-grade dysplasia, high-grade dysplasia, and EA using microdissected paraffin-embedded tissues from 11 patients. Higher levels of miR-196a were observed in EA, BE, and dysplastic lesions compared with normal squamous mucosa, and in high-grade dysplasia compared with BE and lowgrade dysplasia. Using frozen tumor tissues from 10 additional patients who had advanced EA, we evaluated the correlation of miR-196a with its in silicopredicted targets, keratin 5 (KRT5), small prolinerich protein 2C (SPRR2C), and S100 calcium-binding protein A9 (S100A9), which are down-regulated during BE progression. MiR-196a levels inversely correlated with the predicted target mRNA levels in EA. We confirmed that miR-196a specifically targets KRT5, SPRR2C, and S100A9 3′ UTRs using miR-196a-mimic and luciferase reporter-based assays. In conclusion, this study identified miR-196a as a potential marker of progression of BE and KRT5, SPRR2C, and S100A9 as its targets.
UR - http://www.scopus.com/inward/record.url?scp=65649117364&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=65649117364&partnerID=8YFLogxK
U2 - 10.2353/ajpath.2009.080718
DO - 10.2353/ajpath.2009.080718
M3 - Article
C2 - 19342367
AN - SCOPUS:65649117364
SN - 0002-9440
VL - 174
SP - 1940
EP - 1948
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 5
ER -