High miR-96 levels in colorectal adenocarcinoma predict poor prognosis, particularly in patients without distant metastasis at the time of initial diagnosis

Abstract

MicroRNA-96 (miR-96) is an oncomiR that facilitates the development of malignant tumors by promoting growth, proliferation, and survival of cancer cells. Previous studies using high-throughput techniques have shown that miR-96 is upregulated in colorectal cancer compared to adjacent normal colorectal tissue. The aim of this study was the investigation of the potential clinical value of miR-96 as a molecular prognostic biomarker in colorectal adenocarcinoma. For this purpose, total RNA was extracted from 108 primary colorectal adenocarcinoma samples and 54 paired non-cancerous colorectal tissue specimens. After polyadenylation and reverse transcription, miR-96 molecules were determined using an in-house developed real-time quantitative PCR based on SYBR Green chemistry. Calculations were carried out with the comparative C method, using SNORD48 as endogenous reference gene. Finally, extensive biostatistical analysis was performed and showed that miR-96 is significantly upregulated in colorectal adenocarcinoma specimens compared to their non-cancerous counterparts (p < 0.001) as well as in tumors having invaded regional lymph nodes (p = 0.009) and those of advanced TNM stage (p = 0.008). miR-96 expression is an unfavorable prognostic marker in colorectal adenocarcinoma, predicting poor disease-free and overall survival (p = 0.041 and 0.028, respectively), independently of classical clinicopathological parameters. Most importantly, miR-96 expression stratifies patients without distant metastasis (M0) at the time of diagnosis into two groups with substantially different prognosis (p = 0.040). In conclusion, high tissue levels of miR-96 are associated with advanced stages of colorectal adenocarcinoma and predict an increased risk for disease recurrence and poor overall survival, especially in patients without distant metastasis at the time of diagnosis.

Targeting of miR‐31/96/182 to the Numb gene during head and neck oncogenesis

“…The miR‐96 and miR‐182 , members of the miR‐183/96/182 cluster, are oncogenic during a variety of malignancies . The epidermal growth factor receptor pathway has been reported to trans‐activate miR‐96 expression in prostate carcinoma .…”

“…The miR-96 and miR-182, members of the miR-183/96/ 182 cluster, 22 are oncogenic during a variety of malignancies. 12,[23][24][25][26][27][28][29][30][31] The epidermal growth factor receptor pathway has been reported to trans-activate miR-96 expression in prostate carcinoma. 26 High miR-96 expression has been noted in cervical squamous cell carcinoma that is positive for human papillomavirus-16.…”

miR-10b is a prognostic marker in clear cell renal cell carcinoma

“…Accumulating evidence showed miRNA dysregulation with tumour progression. miRNAs can function as metastasis-suppressive or promoting and have been shown to be potential prognostic markers in different cancers 13 14…”

Elevated expression of miR-24-3p is a potentially adverse prognostic factor in colorectal adenocarcinoma

“…In fact, expression levels of specific miRNAs vary significantly among cancerous and non-cancerous colorectal mucosae. Consequently, particular miRNAs with a deregulated expression profile in colorectal adenocarcinoma could provide diagnostic and prognostic biomarkers [19][20][21]. In fact, more than 160 miRNAs have been shown to exhibit an altered expression profile in CRC [22].…”