Abstract

Increasing evidence supports that microRNA (miRNA) plays a significant functional role in cancer progression by directly regulating respective targets. In this study, the expression levels of miR-105-1 and its target gene were analyzed using genes microarray and hierarchical clustering analysis followed by validation with quantitative RT-PCR in hepatocellular carcinoma (HCC) and normal liver tissues. We examined the expression of nuclear receptor coactivator 1 (NCOA1), the potential target gene of miR-105-1, following the transfection of miR-105-1 mimics or inhibitors. Our results showed that miR-105-1 was downregulated in HCC tissues when compared with normal liver tissues and patients with lower miR-105-1 expression had shorter overall survival (OS) and progression free survival (PFS). Moreover, NCOA1 was confirmed to be a direct target of miR-105-1. Furthermore, concomitant high expression of NCOA1 and low expression of miR-105-1 correlated with a shorter median OS and PFS in HCC patients. In conclusion, our results provide the first evidence that NCOA1 is a direct target of miR-105-1 suggesting that NCOA1 and miR-105-1 may have potential prognostic value and may be useful as tumor biomarkers for the diagnosis of HCC patients.

Highlights

  • Hepatocellular carcinoma (HCC) is one of the world’s most common malignant tumors and is characterized by poor prognosis and high mortality rates [1]

  • Our results showed that miR-105-1 was downregulated in hepatocellular carcinoma (HCC) tissues when compared with normal liver tissues and patients with lower miR-1051 expression had shorter overall survival (OS) and progression free survival (PFS)

  • We found 14 upregulated and 24 downregulated miRNAs (fold change (FC) ≥ 2 or ≤ 0.5, P < 0.01) (Figure 1A) in HCC tissues when compared with normal liver tissues

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Summary

INTRODUCTION

Hepatocellular carcinoma (HCC) is one of the world’s most common malignant tumors and is characterized by poor prognosis and high mortality rates [1]. While recent advancements in medical imaging have resulted in early diagnosis of HCC patients, www.impactjournals.com/oncotarget clinical prognosis of HCC remains dire despite the use of targeted therapies [3,4,5]. Previous studies have identified various miRNAs in HCC patients, including miR-1, miR9, miR-15b, miR-130b, miR-16, miR-18a, and miR-21 [10,11,12,13]. MiR-105-1 has been detected in many tumors, such as breast cancer, prostate tumor, human glioma, and gastric cancer [14,15,16,17], its role and clinical significance have not been clarified in HCC. In this study, we explored the clinical significance and target gene of miR-105-1 as a prognostic biomarker for HCC patients

RESULTS
DISCUSSION
Ethics statement
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