Differential expression of microRNA-320a, -145, and -192 along the continuum of normal mucosa to high-grade dysplastic adenomas of the colorectum

Abstract

BACKGROUND MicroRNA (miR)-320a, miR-145, and miR-192 have been shown to play a role in colorectal carcinogenesis and metastasis. We examined if there is a difference in expression during the histologic progression from normal mucosa (NM) to high-grade dysplastic adenomas (HG). METHODS Genome-wide miRNA expression profiling was performed on 113 colon adenomas. Information included histologic type, tumor grade, location, sex, age, family, and smoking history. A 2-way ANOVA was performed to evaluate the effect of the following factors adjusted for scan dates: location, sex, age, family history, smoking, and histology. RESULTS The expression of miR-320a increased; miR-145 and miR-192 expression decreased (P < .0001), with higher histologic grade, and were independent of age, sex, family history, and smoking status. CONCLUSIONS The miRs studied had statistically significant changes in expression with progression of histologic grade. These changes may signify progression of normal mucosa to HG and potentially serve as early markers for disease progression and differentiating high- from low-risk adenomas.

MicroRNA-320 family is downregulated in colorectal adenoma and affects tumor proliferation by targeting CDK6

“…From the results of our comprehensive microarray miRNA analysis, miR-320a, b, c, d and e were downregulated from adenoma to submucosal invasive carcinoma in both LSTs and protruded tumors. It has been previously reported that miR-320a regulates tumor occurrence [20] , progression [21] , and metastasis [22] in CRC; therefore, we inferred that the miR-320 family may play an important role in colo-rectal carcinogenesis [23] . Moreover, 6 of the 10 miRNAs, including the miR-320 family, were identical between the LST-G type and protruded tumors; therefore, there is a possibility that the carcinogenic mechanisms of these two different forms share similar pathways.…”

microRNA-451a regulates colorectal cancer radiosensitivity

“…Several recent studies have shown the utility of miRs in the diagnosis and classification of CRC 7,8,[11][12][13][14] . There are ongoing prospective clinical trials evaluating miR based classifiers such as a 24-miR signature in lung cancer diagnosis 15 (Gensignia) and a miR signature in prostate cancer screening 16 (Exiqon).…”

miR-320a/SP1 negative reciprocal interaction contributes to cell growth and invasion in colorectal cancer

“…Mechanistically, absence of miR-320a in CRC is responsible for enhanced cell growth, invasion, and chemo-resistance via activation of a series of tumor-promoting genes such as RAC1, SOX4, FOXM1, FOXQ1, and Wnt/β-catenin [ 15 , 16 , 20 ]. Notably, a genome-wide miRNA expression profiling-based analysis showed an increased expression pattern of miR-320a in colorectal adenomas with higher histologic grade [ 21 ], which indicates its regulatory effects may be different in the precancerous stage of CRC.…”