Identification of Four Oxidative Stress‐Responsive MicroRNAs, miR‐34a‐5p, miR‐1915‐3p, miR‐638, and miR‐150‐3p, in Hepatocellular Carcinoma

Abstract

Increasing evidence suggests that oxidative stress plays an essential role during carcinogenesis. However, the underlying mechanism between oxidative stress and carcinogenesis remains unknown. Recently, microRNAs (miRNAs) are revealed to be involved in oxidative stress response and carcinogenesis. This study aims to identify miRNAs in hepatocellular carcinoma (HCC) cells which might involve in oxidative stress response. An integrated analysis of miRNA expression signature was performed by employing robust rank aggregation (RRA) method, and four miRNAs (miR-34a-5p, miR-1915-3p, miR-638, and miR-150-3p) were identified as the oxidative stress-responsive miRNAs. Pathway enrichment analysis suggested that these four miRNAs played an important role in antiapoptosis process. Our data also revealed miR-34a-5p and miR-1915-3p, but not miR-150-3p and miR-638, were regulated by p53 in HCC cell lines under oxidative stress. In addition, clinical investigation revealed that these four miRNAs might be involved in oxidative stress response by targeting oxidative stress-related genes in HCC tissues. Kaplan-Meier analysis showed that these four miRNAs were associated with patients' overall survival. In conclusion, we identified four oxidative stress-responsive miRNAs, which were regulated by p53-dependent (miR-34a-5p and miR-1915-3p) and p53-independent pathway (miR-150-3p and miR-638). These four miRNAs may offer new strategy for HCC diagnosis and prognosis.

Oxidative Stress-Responsive MicroRNAs in Heart Injury

“…Growing evidence has confirmed that miRNAs can be considered as potential targets and modulators of oxidative-stress-related pathways [61]. By analysis of miRNA expression signature implicated in oxidative stress-related pathways, several miRNAs were identified and termed as oxidative stress-responsive miRNAs [62]. The increasing number of studies shows that intracellular ROS can either inhibit or induce miRNA expression level, which results in subsequent biological effects through regulation of their direct target genes ( Figure 2) [63].…”

Could Oxidative Stress Regulate the Expression of MicroRNA-146a and MicroRNA-34a in Human Osteoarthritic Chondrocyte Cultures?

“…Accumulating evidence has reported differences in miRNAs expression profiles between normal and OA cartilage samples, demonstrating their role in the development and progression of OA [ 8 , 9 , 10 ]. Recently, some oxidative stress-responsive miRNAs were identified after the treatment of various cell types with H 2 O 2 [ 11 ]; otherwise, cellular mechanisms regulating oxidative stress were fine-tuned by particular miRNAs [ 12 ]. For these reasons, miRNAs seem to be implicated in the articular damage triggered by oxidative stress in OA pathology.…”

Literature-Based Enrichment Insights into Redox Control of Vascular Biology

“…MicroRNA Associations with "Oxidative Stress." On the other hand, if we look at nodes that are connected by a small number of articles such as the nodes for microRNAs in Figure 1, Step 3, we find "MIR23A" [129], "MIR34A" [130], "MIR155" [131], "MIR210" [132], and "MIR106B" [133] being associated in our KB with "oxidative stress" via "6," "4," "3," "2," and "1" articles, respectively.…”