Subsequent studies investigating the role of miR-210 in modulating mitochondrial function have revealed more targets of miR-210 [53–57]. Besides ISCU [54], which was further confirmed, GPD1L [20], COX10 [53], SDHD and NDUFA4 [55] were also identified as direct targets involved in mitochondrial function regulation. In the study by Puissegur et al. [55], A549 cells overexpressing miR-210 exhibited an aberrant mitochondrial phenotype, mRNA expression

profiling analysis linked miR-210 to mitochondrial dysfunction. Interestingly, miR-210 acts not only as a downstream mediator of HIF-1α, it can also promote HIF-1α stability by suppressing GPD1L, producing a positive feedback between HIF-1α and miR-210 [20]. As miR-210 is highly stable, when hypoxic cells undergo reoxygenation, HIF-1α is degraded immediately, but miR-210 remains Selleckchem Eltanexor stable to sustain glycolytic phenotype and inhibit mitochondrial metabolism under normoxia. Such advantage may be utilized by cancer cells, contributing to Warburg effect [57]. Taken together, the above evidence suggests an indisputable role of miR-210 in modulating mitochondrial metabolism,

and facilitating adaptation of cancer cells to hypoxic condition. miR-210 as diagnostic and prognostic biomarker in cancer Early diagnosis and prognosis evaluation of cancer are of vital importance to improve treatment outcome. It is well acknowledged that cancer cells or tissues harbor aberrant miRNA expression Ergoloid profiles compared to normal cells or screening assay tissues, and specific miRNA signature can not only be used for diagnosis but also to classify cancer patients into subgroups with different prognosis guiding individualized treatment [71–77]. Many studies have investigated the role of miR-210 in cancer diagnosis and prognosis, however,

presenting apparently conflicting results. Most evidence showed that miR-210 was up-regulated in many solid tumors, including breast cancer [16, 78–80], head and neck cancer [17, 76], pancreatic cancer [81–83], lung cancer [55, 84–87], renal cancer [23, 88, 89], lymphoma [90], osteosarcoma [91], esophageal cancer [92] as well as ovarian cancer [93]. There are also some inconsistent evidence that miR-210 was deleted in some cases of ovarian cancer [18], and was down-regulated in some cases of esophageal cancer [26], exhibiting the complexity and heterogeneity of cancer. Table 3 enumerates the studies [81, 86, 94–100] investigating the diagnostic value of miR-210, either alone or in combination with other miRNAs, providing the sensitivity and specificity of miR-210 when it was used alone to discriminate cancer from non-cancer.