In addition, they performed prognostic YM155 analysis of pri-miRNAs and predicted target transcripts of prognostic miRNAs, as well as miRNA-processing genes, revealing that identified miRNAs were virtually independent prognostic factors. They also demonstrated that combination of miRNA and target expression could identify patients with the poorest prognosis, showing us the prospect of integrating miRNA and mRNA information for prognosis analysis. Table 4 Studies investigating prognostic value of miR-210 First author Publication year Types of cancer Types of sample RR or HR (high VS low expression level) Selleck EVP4593 Camps [16] 2008 Breast cancer tissue 4.07(PFS), 11.38(OS) Lawrie [90]
2008 Diffuse large B-cell lymphoma serum No significance Gee [17] 2010 Head and neck cancer tissue Not provided Greither [82] 2010 Pancreatic cancer tissue 2.48 Buffa [107] 2011 Breast cancer (ER−) tissue Not provided Radiojicic [78] 2011 Triple-negative breast cancer tissue No significance Rothe [80] 2011
Breast cancer tissue 4.43(RFS) Greither PRI-724 molecular weight [104] 2012 Soft-tissue sarcoma tissue 3.19(PFS)* Toyama [79] 2012 Breast cancer tissue 4.39 Volinia [105] 2012 Breast cancer tissue 1.54(OS) Cai [91] 2013 Pediatric osteosarcoma tissue 2.6(PFS), 3.3(OS) Eilertsen [87] 2013 Non-small cell lung cancer tissue# 1.9(DSS)** McCormick [23] 2013 Renal cancer tissue Not provided Qiu [106] 2013 Glioblastoma tissue 0.75** *intermediate VS high expression level. #stromal cells in tumor tissues. **low VS high expression level. Abbreviations: PFS progression-free survival, OS overall survival, RFS relapse-free survival, DSS disease-specific survival, ER − estrogen receptor negative. Conclusions and future directions As the master HRM, regulated mainly by HIF-1, miR-210 plays an essential role in hypoxic response. In addition to regulating mitochondrial metabolism, miR-210 is involved in regulating cell cycle, cell survival, differentiation, DNA repair as well as immune response. Since hypoxia can influence both cell death and survival [108], it is not surprising that miR-210 PtdIns(3,4)P2 can act both as an oncogene and a tumor suppressor, depending on cellular
context, the extent and duration of hypoxia. A reasonable explanation is that since miRNAs can target hundreds of mRNAs with differential biological functions, the ultimate effect of miR-210 depends on the target mRNAs that are available in certain cells. In addition to multiple targets discussed in this review, many other genes have been identified as miR-210 targets, and more and more potential target genes are emerging [12]. An alternative possibility may be that miR-210 acts as a tumor suppressor at the beginning of tumorigenesis when hypoxia is not significant. However, with the progression of tumor, hypoxia becomes significant, tumor cells evolve, become resistant to hypoxia and adapt well to highly expressed miR-210, then miR-210 switches to an oncogene [19, 29].