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Table 1 Dysregulation of the hypoxia-associated miRNAs modulates tumor angiogenesis, EMT and CSC features

From: The role of hypoxia in the tumor microenvironment and development of cancer stem cell: a novel approach to developing treatment

miRNAs Properties Related cancers Altered expression of miRNAs under hypoxic condition Recognized mechanisms
miR-20 (a,b) Tumor suppressive
Anti-angiogenic, anti-proliferative, anti-invasive [89, 90]
Pro-oncogenic
Stemness preserving [91, 92]
Breast cancer [89]
Osteosarcoma [90]
Gastric cancer [91, 92]
Colon cancer, pancreas cancer, prostate cancer [93]
Down-regulation (miR-20a,b) regulation of VEGF [94]
(miR-20b) Targeting HIF1α and STAT3, and inhibition of VEGF expression and modulate tumor angiogenesis [89, 90]
(miR-20a) Targeting E2F1 and HIPK1, activation of Wnt-β-catenin signaling and sustain self-renewal ability of CSCs [91, 92]
miR-21 Pro-oncogenic
Anti-apoptotic, pro-angiogenic, proliferative, invasive, chemoresistant, stemness preserving [95, 96]
Breast cancer [97, 98]
Pancreatic cancer [96, 99]
Prostate cancer, lung cancer [93]
Head and neck cancer [100]
Colorectal cancer [101,102,103]
Gastric cancer [104, 105]
Up-regulation Decrease of the tumor suppressor  PTEN[106] and PDCD4[103]
Increase expression of VEGF and HIF-1α and tumor angiogenesis [107]
Increase CSC self-renewal capacity [108] and stemness properties [109, 110]
miR-22 Tumor suppressive
Anti-angiogenic, anti-invasive, anti-proliferative, chemosensitive, radiosensitivite, pro-apoptotic [111,112,113,114]
Pro-oncogenic
Metastatic, stemness, preserving [115, 116]
Colon cancer [111]
Hepatocellular carcinoma [112]
Ovarian cancer [113]
Cervical cancer  [114]
Breast cancer [115]
Down-regulation Up-regulation of the tumor suppressor PTEN
Suppression Of P21 And Induction Of P53-Dependent apoptosis [111, 117]
Inhibition of c-Myc binding protein, reduction of human telomerase reverse transcriptase, and increased radiosensitivity [114]
Inhibition of tumor suppressor TET2, increase of Aim2, Hal, Igbt2, and Sp140, and increase EMT and CSC self-renewal and stemness [115]
miR-101 Tumor suppressive
Anti-invasive, stemness inhibitory [118]
Pancreatic cancer [119]
Prostate cancer [120]
Non-small cell lung cancer[121]
Down-regulation Inactivation of epigenetic regulator EZH2, and  inhibition of cancer CSC maintenance and EMT characteristics [119, 122]
miR-107 Tumor suppressive
Anti-angiogenic, chemoresistant, stemness inhibitory [123, 124]
Breast cancer
Colon cancer [125]
Pancreatic cancer [93]
Head and neck cancer [124]
Up-Regulation Regulation of HIF-1β signaling, decrease of VEGF, and inhibition of VEGF mediated angiogenesis [125]
Regulation of protein kinase Cε and stemness [124, 100]
miR-181b Pro-oncogenic [126, 127].
Tumor suppressive
Stemness inhibitory [128, 129]
Acute myeloid leukemia [126]
Hepatocellular carcinoma [127]
Glioblastoma [129]
Non-small cell lung cancer [128]
Up-regulation Inhibition of MLK2 and proliferation of cancer cells [126]
Suppression of TIMP3, enhancement of MMP2 and MMP9 activity, and tumor progression and invasion [127]
Down regulation of Notch2 in CSCs, decrease stem markers,
Suppression of tumorsphere formation, and increases Chemosensitivity related to CSCs [128]
miR-200 (a,b,c) Tumor suppressive
Anti-invasive, stemness inhibitory [118, 130]
Gastric cancer [131]
Breast cancer [132]
Prostate cancer, pancreatic cancer, colon cancer [118]
Nasopharyngeal carcinoma  [130]
Down-regulation Targeting the ZEB1/ZEB2, suppression of Wnt/β-catenin pathway,  increase E-cadherin, and inhibition of EMT[131] and CSC phenotype [132, 133]
Down-regulation of Bmil-1, Suz12, and Notch-1, regulating the CSC and EMT phenotypes and functions and inhibition of CSC formation [118]
Targeting the MYH10, and inhibition of migration and invasion [130]
miR-210 Pro-oncogenic
Pro-angiogenic, proliferative, invasive, metastatic, stemness preserving [134]
Breast cancer [134, 135]
Colon ccancer [136]
Up-regulation Increase of VEGF and CAIX expression, and tumor angiogenesis
Targeting of E-cadherin mRNA, up-regulation of E-cadherin transcription repressor (Snail) and suppression of E-cadherin expression, increase of CSC metastasis, proliferation, and self-renewal capacity [134]
Suppression of RAD52, reduces DNA repair and results in hypoxia-related genetic instability in cancer [137]
miR-373 Pro-oncogenic
Proliferative, invasive, metastatic, stemness preserving [138, 139]
Breast cancer [138]
Colorectal cancer [139]
Up-regulation Transactivation of E-cadherin and metastatic develpment [140, 141]
Activation of Nanog and Hedgehog signaling pathways, and enhancement of cancer cell self-renewal capacity and stemness [139]
Suppression of RAD23B and RAD52, reduces DNA repair and results in hypoxia-related genetic instability in cancer [137]
let-7 (a, b, c, d, e, f, g) Tumor suppressive
Anti-invasive,stemness inhibitory [142,143,144].
Breast cancer [145]
Head and neck cancer [100]
Oral cancer [142]
Prostate cancer [143] Pancreatic cancer [144]
Down-regulation Regulation of PTEN, CSC marker Lin28b, suppression of EMT and CSC phenotype [142,143,144]
Blockage of Wnt signaling and suppressing self-renewal and stemness of CSCs [145]
Inhibition of EZH2, and suppression of CSC characteristics [146]
miR-26a Tumor suppressive
Anti-invasive, stemness inhibitory [147,148,149]
Gastric cancer [150]
Hepatocellular carcinoma [149]
Breast cancer, prostate cancer, pancreatic cancer, nasopharyngeal carcinoma [118]
? Suppression of HOXC9 and inhibits its metastatic and stemness features of self-renewal [150]
Inhibition of EZH2, and suppression of CSC characteristics [147, 148] and EMT [149]