Here we report an integrative meta-analysis and bioinformatics methodology that showed microRNA-21 and its associated target mRNA to be the most significant predictive biomarkers for colorectal adenoma and adenocarcinoma.
The expression of miR-210, miR-21 and miR-126 was performed using qRT-PCR in adenocarcinoma (no = 35), adenomas (no = 51), and neoplasm free controls (no = 101).
In addition, for the first time we have found that miR-21-5p and miR-196a-5p were gradually upregulated from normal to adjacent to tumor tissues; miR-218-5p was gradually downregulated with 2-fold or greater change in AC tissues.
In these paired samples miR-181b-5p was up-regulated in squamous cell carcinoma (SCC), miR-486-5p was down-regulated in adenocarcinoma (AC), and miR-21-5p was up-regulated in both SCC and AC.
An increased expression of miR-21 was found in the tumour-associated stroma with the most dramatic increase from adenoma to adenocarcinoma, while the number of positive miR-145 fibroblast-like cells in the normal lamina propria (stroma) decreased in a stepwise manner throughout the normal-adenoma-adenocarcinoma sequence.
Significant overexpression of miR-21 (p=0.004), miR-27a (p=0.02), miR-34a (p<0.001), miR-196a (p=0.027) and miR-221 (p=0.031) was characteristic of HPV-positive squamous cell carcinomas in contrast to adenocarcinomas of the same HPV status.
When co-cultured with normal fibroblasts, miR-21 expression was elevated in SCC cells (KYSE-30), while its expression was restricted to fibroblasts when co-cultured with adenocarcinoma cells (OE-33 and FLO-1).
In the microarray analyses, 28 miRNAs were upregulated in pancreatic ductal adenocarcinoma compared with normal pancreatic tissue, whereas 48 miRNAs were downregulated. miRNA-21 was the most significantly overexpressed miRNA in the pancreatic ductal adenocarcinomas analyzed, and was also highly expressed in 75% of the 65 pancreatic ductal adenocarcinomas examined by real-time RT-PCR.
Expression levels of miR-143 and miR-21 and correlations with clinicopathological features were analyzed in 26 matched pairs of tumor and adjacent noncancerous tissue samples collected from patients with PCs, including 18 pancreatic ductal adenocarcinomas (PDACs) and 8 adenocarcinomas of Vater's papilla (PVACs).
Resection specimens containing adenocarcinoma (n = 17), intraductal papillary mucinous neoplasms (n = 11), and nonneoplastic tissues (n = 15) were evaluated for miR-21, miR-221, miR-100, miR-155, and miR-181b expression by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and a subset of carcinomas and intraductal papillary mucinous neoplasms was analyzed with miRNA microarrays.
We show SIDT1-mediated intercellular transfer of microRNA-21 to be a driver of resistance to the nucleoside analog gemcitabine in human adenocarcinoma cells.
Analysis of the Akt2/miR-21 pathway in hypoxic MMTV-PyMT-induced mouse mammary adenocarcinomas and human ovarian carcinomas confirmed the activity of the pathway in vivo.