Quantitation of microRNA-92a in colorectal adenocarcinoma and its precancerous lesions: Co-utilization of in situ hybridization and spectral imaging

Abstract

The expression level of microRNA (miR)-92a has been proven to increase during the development of colorectal adenocarcinoma (CA) and has been verified at the cellular, plasma and fecal levels by various quantitative methods. However, a method to quantitate the expression level using tissue sections has not been established. To do this, in situ hybridization (ISH) and multispectral imaging microscopy (MSI) were introduced to quantitate miR-92a expression on the microscopic level. ISH of miR-92a was first performed on 34 tissue samples of CA and adenomas with high-grade and low-grade intraepithelial neoplasms, while 31 paralesional normal tissue samples were defined as the control. Subsequently, a MSI technique was applied to quantitate the hybridization signal in terms of optical density (OD) at the visible wavelength. A t-test with unequal variance was used to examine the statistical significance between the groups. Despite all 34 tissue sections demonstrating at least partial positivity of miR-92a expression following ISH, visual grading was inconclusive. As such, the signal of ISH was transformed in terms of OD and further analyzed by employing the MSI system. A statistically significant difference was observed between the expression levels of miR-92a in CA and the paralesional normal controls. By contrast, a poor correlation was revealed between visual and spectral grading. The co-utilization of ISH and MSI generated a legible observation in the expression level of miR-92a, revealing the dynamic change in miR-92a expression in the progression of the disease and providing important information for further functional investigation.

Comparative effects of diet and carcinogen on microRNA expression in the stem cell niche of the mouse colonic crypt

“…We observed that miR-92a, a well-characterized oncomiR in colorectal cancer (90–94) was upregulated in stem cells, while miR-124 a tumor suppressor in colorectal cancer was downregulated in stem cells as compared to differentiated cells (95–97). Interestingly, other members of miR-17-92, e.g., miR-18a and miR-20b, were also upregulated in AOM-Lgr5 negative cells.…”

A microRNA-based prediction model for lymph node metastasis in hepatocellular carcinoma

“…MiR-92a expression levels were scored using the following four-tier scoring system according to the staining intensity: 0 = negative, 1 = weak positive, 2 = moderate and 3 = strong positive. Expression levels were considered as negative, final score ≤ 0.5 or positive 0.5 < final score ≤ 3 [ 16 ]. Cytoplasmic miR-10b staining was categorized as follows: low-expression, < 20 % of cells stained; high-expression, ≥ 20 % of cells stained [ 17 ].…”

MicroRNA-92a Inhibits the Cell Viability and Metastasis of Prostate Cancer by Targeting SOX4

“…In the studies of colorectal cancer, hepatocellular carcinoma, pancreatic cancer, cervical cancer and osteosarcoma, miR-92a was reported to exert oncogenic influence on cancer progression. [9][10][11][12][13][14] However, our data revealed a tumor suppressive role of miR-92a in PCa using both gain-and loss-of function assays. These indicate that the functional influence of miR-92a in human cancers differs in different types of human cancers.…”

“… 6 They were proposed as the promising biomarkers and therapeutic targets of human cancers including PCa. 7 , 8 Recent studies reported that miR-92a played critical roles in the progression of colorectal cancer, 9 , 10 hepatocellular carcinoma, 11 pancreatic cancer, 12 cervical cancer 13 and osteosarcoma. 14 It was found to promote the proliferation, metastasis, and metabolism of cancer cells and its expression levels in cancer tissues was correlated with the clinical prognosis of patients.…”