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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]