Fig. 11

Summary figure. The continuous arrows show findings derived from our results while the dotted arrows represent the summary obtained from previous published works. Under hypoxia microenvironment, HIF-1α was upregulated similar to its downstream targets associated with stemness (SOX2, OCT4), metabolism (GLUT-1), angiogenesis (VEGF), EMT transitioning (Vimentin) and anti-apoptosis (Bcl-2, survivin). The miR-34, 128 and 181 were found downregulated from our study similar to what has been reported. Previous works have associated the same miRNAs with key tumour suppressor or oncogenes which can also influence their activation directly or indirectly. Additionally, the miRNAs can also influence the expression of the tumour suppressor or oncogenes. In this manner, miR-34 has been reported to target multiple oncogenes including c-MET, NOTCH 1 and 2, BCL-2 and CDK6 in gliomas. Additionally, P53 has been shown to influence miR-34 expression. An oncogene c-myc has also been reported to directly activate the transcription of miR-17 family. Oncogenic signalling pathways, such as those of Notch and Sonic Hedgehog, have also been shown to activate miR-17-92 in cancer. Most of the key tumour’s suppressors are known to have loss of function mutations that could also influence the expression of the miRNAs and the HIF. That means HIF-1α can also be subjected to the negative regulation by tumour suppressors such as Von Hippel-Lindau (VHL) and (PTEN). Additionally, some miRNAs can regulate the tumour suppressors that negatively regulate the HIF-1α. This has been shown by a study that found that MiR-17 induced HIF-1α activation in response to stress by targeting PTEN in GBM cells. Also, p53 that acts as negative transcriptional regulator of the miR-17-92 cluster under hypoxia is found mutated in the GBM