Date Published: July 25, 2017
Publisher: Public Library of Science
Author(s): Xianxiong Ma, Jie Bai, Gengchen Xie, Yulin Liu, Xiaoming Shuai, Kaixiong Tao, Burton B Yang.
MicroRNA-101 has been reported as an important factor in carcinogenesis of several malignant tumors. However, its actual role in prognosis among solid malignancies remains unclear. Accordingly, we performed this meta-analysis aiming to identify prognostic significance of miR-101 in solid tumor. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) or disease-free survival (DFS)/metastasis-free survival (MFS)/progression-free survival (PFS)/relapse-free survival (RFS)/time-to progression (TTP) were estimated with random effects or fixed effects models on the basis of heterogeneity. Subgroup analysis, sensitive analysis and meta-regression analysis were also conducted to clarify the possible confounding factors and investigate the source of heterogeneity. Publication bias was evaluated by using Begg’s and Egger’s tests. A total of 21 studies containing 3753 cases were selected into our quantitative analysis via electronic database search. A lower expression of miR-101 was significantly associated with worse OS (HR = 0.66, 95%CI [0.52–0.85], P = 0.001) and PFS (HR = 0.70, 95%CI [0.51–0.95], P = 0.023) in patients with solid tumor. The under-expression of miRNA-101 is a credible indicator of poorer prognosis in several of solid malignancies.
MicroRNAs (miRNA, miRs) are a subset of small non-coding RNA molecules that are approximately 18–22 nucleotides in length. MiRNAs play crucial regulatory roles in gene expression at the post-transcriptional level [1, 2]. The major mechanism of miRNA action is the interaction with the 3’-UTR of the targeted gene mRNA, followed by degradation of the mRNA or inhibition of mRNA protein translation. In human cancers, numerous studies have shown that the expression of miRNAs is deregulated and these miRNAs act as regulatory molecules in many biological processes, including differentiation, proliferation, and apoptosis of tumor cells [3–5]. Several miRNAs are downregulated in many tumors and appear to function as tumor suppressor genes . Among these downregulated miRNAs, miR-101 is one of the most downregulated miRNAs in human cancers, multiple research studies have been exploring the prognostic function of miR-101 in cancer patients in order to find a reliable biomarker to guide for cancer treatment[7, 8].
Numerous profiling studies have demonstrated that miRNA expression levels failed to agree in various types of cancers, miRNAs can be potential biomarkers for cancer prognosis. Increasing data favor the potential use of miR-101 as a cancer prognostic predictor. Recently, genome-wide miRNA expression profiling studies revealed that miR-101 is widely present in various tissues and organs, and its aberrant expression was reported in various cancers including HCC[14, 19, 20, 25], CRC[13, 30], breast cancer[23, 26], NSCLC, gliomas, and et al. It is indubitable that miR-101 is an important cancer-related miRNA. More and more evidence has demonstrated that miR-101 is frequently downregulated in multiple types of cancer and acts as a tumor suppressor by repressing many critical oncogenes. In hepatocellular carcinoma, Wang et al found c-Myc collaborates with EZH2-containing PRC2 complex in silencing miRNA-101 during hepatocarcinogenesis and lower expression of miR-101 is positively correlated with poorer prognosis . In CRC, it is reported that loss of miR-101 expression promotes Wnt/β-catenin signaling pathway activation and malignancy in colon cancer cells. Similarly, in glioblastoma, Liu et al demonstrated that miRNA-101 inhibits proliferation, migration and invasion of glioblastoma by targeting SOX9 , Michiel et al also found that miRNA-101 is down-regulated in glioblastoma resulting in EZH2-induced proliferation, migration, and angiogenesis . Moreover, miRNA-101 reverses temozolomide resistance by inhibition of GSK3β in glioblastoma. In nasopharyngeal carcinoma, MicroRNA-101 inhibits invasion and angiogenesis through targeting ITGA3 and its systemic delivery inhibits lung metastasis. On the other hand, 175 targeted genes validated by experiment and 5206 targeted genes predicted by miRanda software can be found in GCBI website based on classical miRNA-3’-UTR pathway (https://www.gcbi.com.cn/gclib/html/dictSearchAct/MI0000103/miRNA), indicating miRNA-101 may play a complicated role in many gene ontology functions and pathways networks. Further experiments need to be conducted to elucidate the role of miR-101 in carcinogenesis. However, among all the studies referring to the relationship between miRNA-101 and OS/PFS, there were still some contradictory views requiring adequate attention, a comprehensive study is therefore in urgent.