Role of MicroRNA in Hypoxic Tumours and their Potential as
Biomarkers for Early Detection of Cancer

Pawar      Jayashree; Mulye      Kalpita; Talker      Judith; Ahirwar   Sonu   Singh; Kotnis      Ashwin
doi:10.2174/0115665240268661231128094831
Abstract

Hypoxia is a pathophysiological condition characterized by oxygen deficiency in tissues, which negatively affects normal biological functions. It is a typical microenvironment character of almost all solid tumours. Noncoding RNA are small functional RNA molecules that regulate gene expression at chromatin and posttranscriptional levels. Micro-RNAs (miRNAs) are a type of noncoding RNA and are ~12-22 nucleotides long that are crucial in regulating gene expression by partnering with the mRNAs of protein-coding genes. It is widely reported that miRs play an important role in various key processes and pathways during tumour formation, as well as advancement in hypoxic tumors by influencing the HIF pathway. The role of miRNAs in hypoxic tumours, namely in pancreatic, kidney, breast, lung and colorectal, are described. These miRNAs have immense potential as diagnostic and prognostic biomarkers for early cancer detection.
Keywords: microRNA, ncRNA, hypoxia, biomarker, cancer, diagnosis, prognosis.
[1]
Qian D, Xie Y, Huang M, Gu J. Tumor-derived exosomes in hypoxic microenvironment: Release mechanism, biological function and clinical application. J Cancer  2022; 13(5): 1685-94.
 [http://dx.doi.org/10.7150/jca.69278] [PMID: 35371323]

[2]
Walsh JC, Lebedev A, Aten E, Madsen K, Marciano L, Kolb HC. The clinical importance of assessing tumor hypoxia: Relationship of tumor hypoxia to prognosis and therapeutic opportunities. Antioxid Redox Signal  2014; 21(10): 1516-54.
 [http://dx.doi.org/10.1089/ars.2013.5378] [PMID: 24512032]

[3]
Bhandari V, Hoey C, Liu LY, et al. Molecular landmarks of tumor hypoxia across cancer types. Nat Genet  2019; 51(2): 308-18.
 [http://dx.doi.org/10.1038/s41588-018-0318-2] [PMID: 30643250]

[4]
Farina AR, Cappabianca L, Sebastiano M, Zelli V, Guadagni S, Mackay AR. Hypoxia-induced alternative splicing: The 11th Hallmark of Cancer. J Exp Clin Cancer Res  2020; 39(1): 110.
 [http://dx.doi.org/10.1186/s13046-020-01616-9] [PMID: 32536347]

[5]
Pressley M, Gallaher JA, Brown JS, et al. Cycling hypoxia selects for constitutive HIF stabilization. Sci Rep  2021; 11(1): 5777.
 [http://dx.doi.org/10.1038/s41598-021-85184-8] [PMID: 33707510]

[6]
Muz B, de la Puente P, Azab F, Azab AK. The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy. Hypoxia  2015; 3: 83-92.
 [http://dx.doi.org/10.2147/HP.S93413] [PMID: 27774485]

[7]
Thirlwell C, Schulz LKE, Dibra HK, Beck S. Suffocating cancer: Hypoxia-associated epimutations as targets for cancer therapy. Clin Epigenetics  2011; 3(1): 9.
 [http://dx.doi.org/10.1186/1868-7083-3-9] [PMID: 22414300]

[8]
Geismann C, Arlt A. Coming in the air: Hypoxia meets epigenetics in pancreatic cancer. Cells  2020; 9(11): 2353.
 [http://dx.doi.org/10.3390/cells9112353] [PMID: 33113836]

[9]
Barreca MM, Zichittella C, Alessandro R, Conigliaro A. Hypoxia-induced non-coding RNAs controlling cell viability in cancer. Int J Mol Sci  2021; 22(4): 1857.
 [http://dx.doi.org/10.3390/ijms22041857] [PMID: 33673376]

[10]
Schmid T, Zhou J, Brüne B. HIF-1 and p53: Communication of transcription factors under hypoxia. J Cell Mol Med  2004; 8(4): 423-31.
 [http://dx.doi.org/10.1111/j.1582-4934.2004.tb00467.x] [PMID: 15601571]

[11]
Koshiji M, Huang LE. Dynamic balancing of the dual nature of HIF-1alpha for cell survival. Cell Cycle  2004; 3(7): 851-2.
 [http://dx.doi.org/10.4161/cc.3.7.989] [PMID: 15190211]

[12]
Kaplan AR, Glazer PM. Impact of hypoxia on DNA repair and genome integrity. Mutagenesis  2020; 35(1): 61-8.
 [http://dx.doi.org/10.1093/mutage/gez019] [PMID: 31282537]

[13]
Ye Y, Hu Q, Chen H, et al. Characterization of hypoxia-associated molecular features to aid hypoxia-targeted therapy. Nat Metab  2019; 1(4): 431-44.
 [http://dx.doi.org/10.1038/s42255-019-0045-8] [PMID: 31984309]

[14]
Gong PJ, Shao YC, Huang SR, et al. Hypoxia-associated prognostic markers and competing endogenous RNA Co-Expression networks in breast cancer. Front Oncol  2020; 10: 579868.
 [http://dx.doi.org/10.3389/fonc.2020.579868] [PMID: 33344235]

[15]
Sharma PC, Gupta A. MicroRNAs: Potential biomarkers for diagnosis and prognosis of different cancers. Transl Cancer Res  2020; 9(9): 5798-818.
 [http://dx.doi.org/10.21037/tcr-20-1294] [PMID: 35117940]

[16]
Allegra A, Alonci A, Campo S, et al. Circulating microRNAs: New biomarkers in diagnosis, prognosis and treatment of cancer. (Review) Int J Oncol  2012; 41(6): 1897-912.
 [http://dx.doi.org/10.3892/ijo.2012.1647] [PMID: 23026890]

[17]
Lee AH, Mejia Peña C, Dawson MR. Comparing the secretomes of chemorefractory and chemoresistant ovarian cancer cell populations. Cancers  2022; 14(6): 1418.
 [http://dx.doi.org/10.3390/cancers14061418] [PMID: 35326569]

[18]
Condrat CE, Thompson DC, Barbu MG, et al. miRNAs as biomarkers in disease: Latest findings regarding their role in diagnosis and prognosis. Cells  2020; 9(2): 276.
 [http://dx.doi.org/10.3390/cells9020276] [PMID: 31979244]

[19]
Wang H, Peng R, Wang J, Qin Z, Xue L. Circulating microRNAs as potential cancer biomarkers: The advantage and disadvantage. Clin Epigenetics  2018; 10(1): 59.
 [http://dx.doi.org/10.1186/s13148-018-0492-1] [PMID: 29713393]

[20]
Cheng HH, Mitchell PS, Kroh EM, et al. Circulating microRNA profiling identifies a subset of metastatic prostate cancer patients with evidence of cancer-associated hypoxia. PLoS One  2013; 8(7): e69239.
 [http://dx.doi.org/10.1371/journal.pone.0069239] [PMID: 23935962]

[21]
Shiotani A, Murao T, Kimura Y, et al. Identification of serum miRNAs as novel non-invasive biomarkers for detection of high risk for early gastric cancer. Br J Cancer  2013; 109(9): 2323-30.
 [http://dx.doi.org/10.1038/bjc.2013.596] [PMID: 24104965]

[22]
Qiu X, Zhang J, Shi W, et al. Circulating MicroRNA-26a in plasma and its potential diagnostic value in gastric cancer. PLoS One  2016; 11(3): e0151345.
 [http://dx.doi.org/10.1371/journal.pone.0151345] [PMID: 27010210]

[23]
Shekari N, Baradaran B, Shanehbandi D, Kazemi T. Circulating MicroRNAs: Valuable biomarkers for the diagnosis and prognosis of gastric cancer. Curr Med Chem  2018; 25(6): 698-714.
 [http://dx.doi.org/10.2174/0929867324666171003123425] [PMID: 28971758]

[24]
Palmirotta R, Lovero D, Cafforio P, et al. Liquid biopsy of cancer: a multimodal diagnostic tool in clinical oncology. Ther Adv Med Oncol  2018; 10.
 [http://dx.doi.org/10.1177/1758835918794630] [PMID: 30181785]

[25]
Matin F, Jeet V, Moya L, et al. A plasma biomarker panel of four MicroRNAs for the diagnosis of prostate cancer. Sci Rep  2018; 8(1): 6653.
 [http://dx.doi.org/10.1038/s41598-018-24424-w] [PMID: 29703916]

[26]
Panigrahi GK, Ramteke A, Birks D, et al. Exosomal microRNA profiling to identify hypoxia-related biomarkers in prostate cancer. Oncotarget  2018; 9(17): 13894-910.
 [http://dx.doi.org/10.18632/oncotarget.24532] [PMID: 29568403]

[27]
Zhang X, Wang Q, Zhang S. MicroRNAs in sputum specimen as noninvasive biomarkers for the diagnosis of nonsmall cell lung cancer. Medicine  2019; 98(6): e14337.
 [http://dx.doi.org/10.1097/MD.0000000000014337] [PMID: 30732158]

[28]
Hansen TF, Carlsen AL, Heegaard NHH, Sørensen FB, Jakobsen A. Changes in circulating microRNA-126 during treatment with chemotherapy and bevacizumab predicts treatment response in patients with metastatic colorectal cancer. Br J Cancer  2015; 112(4): 624-9.
 [http://dx.doi.org/10.1038/bjc.2014.652] [PMID: 25584492]

[29]
Lindholm EM. miRNA expression changes during the course of neoadjuvant bevacizumab and chemotherapy treatment in breast cancer. Mol Oncol  2019; 13(10): 2278-96.
 [http://dx.doi.org/10.1002/1878-0261.12561]

[30]
Tiberio P, Callari M, Angeloni V, Daidone MG, Appierto V. Challenges in using circulating miRNAs as cancer biomarkers. BioMed Res Int  2015; 2015: 1-10.
 [http://dx.doi.org/10.1155/2015/731479] [PMID: 25874226]

[31]
Panvongsa W, Pegtel DM, Voortman J. More than a bubble: Extracellular vesicle micrornas in head and neck squamous cell carcinoma. Cancers  2022; 14(5): 1160.
 [http://dx.doi.org/10.3390/cancers14051160] [PMID: 35267467]

[32]
Correia CN, Nalpas NC, McLoughlin KE, et al. Circulating microRNAs as potential biomarkers of infectious disease. Front Immunol  2017; 8: 118.
 [http://dx.doi.org/10.3389/fimmu.2017.00118] [PMID: 28261201]

[33]
Cui M, Wang H, Yao X, et al. Circulating MicroRNAs in cancer: Potential and challenge. Front Genet  2019; 10: 626.
 [http://dx.doi.org/10.3389/fgene.2019.00626] [PMID: 31379918]

[34]
Kno. The promise of liquid biopsies for cancer diagnosis. Evid Based Oncol  2021; 27(7): SP261-2.

[35]
Zhou Z, Wu Q, Yan Z, et al. Extracellular RNA in a single droplet of human serum reflects physiologic and disease states. Proc Natl Acad Sci  2019; 116(38): 19200-8.
 [http://dx.doi.org/10.1073/pnas.1908252116] [PMID: 31481608]

[36]
Saliminejad K, Khorram Khorshid HR, Ghaffari SH. Why have microRNA biomarkers not been translated from bench to clinic? Future Oncol  2019; 15(8): 801-3.
 [http://dx.doi.org/10.2217/fon-2018-0812] [PMID: 30652506]

[37]
Mace TA, Collins AL, Wojcik SE, Croce CM, Lesinski GB, Bloomston M. Hypoxia induces the overexpression of microRNA-21 in pancreatic cancer cells. J Surg Res  2013; 184(2): 855-60.
 [http://dx.doi.org/10.1016/j.jss.2013.04.061] [PMID: 23726431]

[38]
Zhu G, Zhou L, Liu H, Shan Y, Zhang X. MicroRNA-224 promotes pancreatic cancer cell proliferation and migration by targeting the TXNIP-mediated HIF1α pathway. Cell Physiol Biochem  2018; 48(4): 1735-46.
 [http://dx.doi.org/10.1159/000492309]

[39]
Daoud AZ, Mulholland EJ, Cole G, McCarthy HO. MicroRNAs in Pancreatic Cancer: biomarkers, prognostic, and therapeutic modulators. BMC Cancer  2019; 19(1): 1130.
 [http://dx.doi.org/10.1186/s12885-019-6284-y] [PMID: 31752758]

[40]
Fathi M, Ghafouri-Fard S, Abak A. Emerging roles of miRNAs in thedevelopment of pancreatic cancer. Biomedicine &. Pharmacotherapy  2021; 141: 111914.
 [http://dx.doi.org/10.1016/j.biopha.2021.111914] [PMID: 34328099]

[41]
Yue H, Liu L, Song Z. miR 212 regulated by HIF-1α promotes the progression of pancreatic cancer. Exp Ther Med  2019; 17(3): 2359-65.
 [http://dx.doi.org/10.3892/etm.2019.7213] [PMID: 30867721]

[42]
Peng X, Guo C, Wu Y, et al. miR 224 5p regulates the proliferation, migration and invasion of pancreatic mucinous cystadenocarcinoma by targeting PTEN. Mol Med Rep  2021; 23(5): 346.
 [http://dx.doi.org/10.3892/mmr.2021.11985] [PMID: 33760113]

[43]
Lou W, Liu J, Gao Y, et al. MicroRNA regulation of liver cancer stem cells. Am J Cancer Res  2018; 8(7): 1126-41.
 [PMID: 30094089]

[44]
Cao W, Zeng Z, He Z, Lei S. Hypoxic pancreatic stellate cell-derived exosomal mirnas promote proliferation and invasion of pancreatic cancer through the PTEN/AKT pathway. Aging  2021; 13(5): 7120-32.
 [http://dx.doi.org/10.18632/aging.202569] [PMID: 33653966]

[45]
Ho AS, Huang X, Cao H, et al. Circulating miR-210 as a novel hypoxia marker in pancreatic cancer. Transl Oncol  2010; 3(2): 109-13.
 [http://dx.doi.org/10.1593/tlo.09256] [PMID: 20360935]

[46]
Papaconstantinou IG, Manta A, Gazouli M, et al. Expression of microRNAs in patients with pancreatic cancer and its prognostic significance. Pancreas  2013; 42(1): 67-71.
 [http://dx.doi.org/10.1097/MPA.0b013e3182592ba7] [PMID: 22850622]

[47]
Abue M, Yokoyama M, Shibuya R, et al. Circulating miR-483-3p and miR-21 is highly expressed in plasma of pancreatic cancer. Int J Oncol  2015; 46(2): 539-47.
 [http://dx.doi.org/10.3892/ijo.2014.2743] [PMID: 25384963]

[48]
Chen F, Chu L, Li J, et al. Hypoxia induced changes in miRNAs and their target mRNAs in extracellular vesicles of esophageal squamous cancer cells. Thorac Cancer  2020; 11(3): 570-80.
 [http://dx.doi.org/10.1111/1759-7714.13295] [PMID: 31922357]

[49]
Braga EA, Fridman MV, Loginov VI, Dmitriev AA, Morozov SG. Molecular mechanisms in clear cell renal cell carcinoma: Role of mirnas and hypermethylated mirna genes in crucial oncogenic pathways and processes. Front Genet  2019; 10: 320.
 [http://dx.doi.org/10.3389/fgene.2019.00320] [PMID: 31110513]

[50]
Grange C, Brossa A, Bussolati B. Extracellular vesicles and carried miRNAs in the progression of renal cell carcinoma. Int J Mol Sci  2019; 20(8): 1832.
 [http://dx.doi.org/10.3390/ijms20081832] [PMID: 31013896]

[51]
Chen SC, Chen FW, Hsu YL, Kuo PL. Systematic analysis of transcriptomic profile of renal cell carcinoma under long-term hypoxia using next-generation sequencing and bioinformatics. Int J Mol Sci  2017; 18(12): 2657.
 [http://dx.doi.org/10.3390/ijms18122657] [PMID: 29215599]

[52]
Wu TK, Wei CW, Pan YR, Hsu RJ, Wu CY, Yu YL. The uremic toxin p-cresylsulfate induces proliferation and migration of clear cell renal cell carcinoma via microRNA-21/HIF-1α axis signals. Sci Rep  2019; 9(1): 1-10.
 [PMID: 30626917]

[53]
Nofech-Mozes R, Khella HWZ, Scorilas A, et al. Micro RNA 194 is a marker for good prognosis in clear cell renal cell carcinoma. Cancer Med  2016; 5(4): 656-64.
 [http://dx.doi.org/10.1002/cam4.631] [PMID: 26860079]

[54]
Dias F, Teixeira AL, Ferreira M, et al. Plasmatic miR-210, miR-221 and miR-1233 profile: Potential liquid biopsies candidates for renal cell carcinoma. Oncotarget  2017; 8(61): 103315-26.
 [http://dx.doi.org/10.18632/oncotarget.21733] [PMID: 29262564]

[55]
Meng L, Xing Z, Guo Z, Qiu Y, Liu Z. Hypoxia-induced microRNA-155 overexpression in extracellular vesicles promotes renal cell carcinoma progression by targeting FOXO3. Aging  2021; 13(7): 9613-26.
 [http://dx.doi.org/10.18632/aging.202706] [PMID: 33742606]

[56]
Huang J, Yao X, Zhang J, et al. Hypoxia induced downregulation of mi R 30c promotes epithelial mesenchymal transition in human renal cell carcinoma. Cancer Sci  2013; 104(12): 1609-17.
 [http://dx.doi.org/10.1111/cas.12291] [PMID: 24112779]

[57]
Yersal O, Barutca S. Biological subtypes of breast cancer: Prognostic and therapeutic implications. World J Clin Oncol  2014; 5(3): 412-24.
 [http://dx.doi.org/10.5306/wjco.v5.i3.412] [PMID: 25114856]

[58]
Vaupel P. The role of hypoxia-induced factors in tumor progression. Oncologist  2004; 9(S5): 10-7.
 [http://dx.doi.org/10.1634/theoncologist.9-90005-10] [PMID: 15591418]

[59]
Niu Y, Bao L, Chen Y, et al. HIF2-Induced long noncoding RNA rab11b-AS1 Promotes hypoxia-mediated angiogenesis and breast cancer metastasis. Cancer Res  2020; 80(5): 964-75.
 [http://dx.doi.org/10.1158/0008-5472.CAN-19-1532] [PMID: 31900259]

[60]
Wong CCL, Gilkes DM, Zhang H, et al. Hypoxia-inducible factor 1 is a master regulator of breast cancer metastatic niche formation. Proc Natl Acad Sci  2011; 108(39): 16369-74.
 [http://dx.doi.org/10.1073/pnas.1113483108] [PMID: 21911388]

[61]
Morotti M, Bridges E, Valli A, et al. Hypoxia-induced switch in SNAT2/SLC38A2 regulation generates endocrine resistance in breast cancer. Proc Natl Acad Sci  2019; 116(25): 12452-61.
 [http://dx.doi.org/10.1073/pnas.1818521116] [PMID: 31152137]

[62]
Mahajan M, Sitasawad S. miR-140-5p attenuates hypoxia-induced breast cancer progression by targeting Nrf2/HO-1 axis in a keap1 independent mechanism. Cells  2021; 11(1): 12.
 [http://dx.doi.org/10.3390/cells11010012] [PMID: 35011574]

[63]
Elghoroury EA, ElDine HG, Kamel SA, et al. Evaluation of miRNA-21 and miRNA Let-7 as prognostic markers in patients with breast cancer. Clin Breast Cancer  2018; 18(4): e721-6.
 [http://dx.doi.org/10.1016/j.clbc.2017.11.022] [PMID: 29292183]

[64]
He J, Wang J, Li S, Li T, Chen K, Zhang S. Hypoxia inhibited miR-338-3p suppresses breast cancer progression by directly targeting ZEB2. Cancer Sci  2020; 111(10): 3550-63.
 [http://dx.doi.org/10.1111/cas.14589] [PMID: 32726486]

[65]
Jiang Y, Zhang M, Yu D, Hou G, Wu J, Li F. CircRBM33 downregulation inhibits hypoxia-induced glycolysis and promotes apoptosis of breast cancer cells via a microRNA-542-3p/HIF-1α axis. Cell Death Discov  2022; 8(1): 126.
 [http://dx.doi.org/10.1038/s41420-022-00860-6] [PMID: 35318311]

[66]
Kashyap D, Kaur H. Cell-free miRNAs as non-invasive biomarkers in breast cancer: Significance in early diagnosis and metastasis prediction. Life Sci  2020; 246: 117417.
 [http://dx.doi.org/10.1016/j.lfs.2020.117417] [PMID: 32044304]

[67]
Grimaldi AM, Incoronato M. Clinical translatability of “identified” circulating mirnas for diagnosing breast cancer: Overview and update. Cancers  2019; 11(7): 901.
 [http://dx.doi.org/10.3390/cancers11070901] [PMID: 31252695]

[68]
Drakaki A, Hatziapostolou M, Iliopoulos D. Therapeutically targeting microRNAs in liver cancer. Curr Pharm Des  2012; 19(7): 1180-91.
 [http://dx.doi.org/10.2174/138161213804805658] [PMID: 23092338]

[69]
Onishi M, Ochiya T, Tanaka Y. MicroRNA and liver cancer. Cancer Drug Resist  2020; 3(3): 385-400.
 [http://dx.doi.org/10.20517/cdr.2019.110] [PMID: 35582451]

[70]
Vaupel P, Höckel M, Mayer A. Detection and characterization of tumor hypoxia using pO2 histography. Antioxid Redox Signal  2007; 9(8): 1221-36.
 [http://dx.doi.org/10.1089/ars.2007.1628] [PMID: 17536958]

[71]
McKeown SR. Defining normoxia, physoxia and hypoxia in tumours—implications for treatment response. Br J Radiol  2014; 87(1035): 20130676.
 [http://dx.doi.org/10.1259/bjr.20130676] [PMID: 24588669]

[72]
Yao B, Li Y, Niu Y, et al. Hypoxia-induced miR 3677 3p promotes the proliferation, migration and invasion of hepatocellular carcinoma cells by suppressing SIRT5. J Cell Mol Med  2020; 24(15): 8718-31.
 [http://dx.doi.org/10.1111/jcmm.15503] [PMID: 32596968]

[73]
Matsuura Y, Wada H, Eguchi H, et al. Exosomal miR-155 derived from hepatocellular carcinoma cells under hypoxia promotes angiogenesis in endothelial cells. Dig Dis Sci  2019; 64(3): 792-802.
 [http://dx.doi.org/10.1007/s10620-018-5380-1] [PMID: 30465177]

[74]
Chang Y, Yan W, He X, et al. miR-375 inhibits autophagy and reduces viability of hepatocellular carcinoma cells under hypoxic conditions. Gastroenterology  2012; 143(1): 177-187.e8.
 [http://dx.doi.org/10.1053/j.gastro.2012.04.009] [PMID: 22504094]

[75]
Méndez-Blanco C, Fernández-Palanca P, Fondevila F, González-Gallego J, Mauriz JL. Prognostic and clinicopathological significance of hypoxia-inducible factors 1α and 2α in hepatocellular carcinoma: A systematic review with meta-analysis. Ther Adv Med Oncol  2021; 13.
 [http://dx.doi.org/10.1177/1758835920987071] [PMID: 33613697]

[76]
Linck-Paulus L, Hellerbrand C, Bosserhoff AK, Dietrich P. Dissimilar appearances are deceptive-common micrornas and therapeutic strategies in liver cancer and melanoma. Cells  2020; 9(1): 114.
 [http://dx.doi.org/10.3390/cells9010114] [PMID: 31906510]

[77]
Callegari E, Gramantieri L, Domenicali M, D’Abundo L, Sabbioni S, Negrini M. MicroRNAs in liver cancer: A model for investigating pathogenesis and novel therapeutic approaches. Cell Death Differ  2015; 22(1): 46-57.
 [http://dx.doi.org/10.1038/cdd.2014.136] [PMID: 25190143]

[78]
Tang XL, Lin L, Song LN, Tang XH. Hypoxia-inducible miR-152 suppresses the expression of WNT1 and ERBB3, and inhibits the proliferation of cervical cancer cells. Exp Biol Med  2016; 241(13): 1429-37.
 [http://dx.doi.org/10.1177/1535370215610442] [PMID: 26515145]

[79]
Mishra GA, Pimple SA, Shastri SS. An overview of prevention and early detection of cervical cancers. Indian J Med Paediatr Oncol  2011; 32(3): 125-32.
 [http://dx.doi.org/10.4103/0971-5851.92808] [PMID: 22557777]

[80]
Lyng H, Malinen E. Hypoxia in cervical cancer: From biology to imaging. Clin Transl Imaging  2017; 5(4): 373-88.
 [http://dx.doi.org/10.1007/s40336-017-0238-7] [PMID: 28804704]

[81]
Kilic S, Cracchiolo B, Gabel M, Haffty B, Mahmoud O. The relevance of molecular biomarkers in cervical cancer patients treated with radiotherapy. Ann Transl Med  2015; 3(18): 261.
 [http://dx.doi.org/10.3978/j.issn.2305-5839.2015.10.18] [PMID: 26605307]

[82]
Nilsen A, Jonsson M, Aarnes EK, Kristensen GB, Lyng H. Reference MicroRNAs for RT-qPCR assays in cervical cancer patients and their application to studies of hpv16 and hypoxia biomarkers. Transl Oncol  2019; 12(3): 576-84.
 [http://dx.doi.org/10.1016/j.tranon.2018.12.010] [PMID: 30660934]

[83]
Gao Q, Ren Z, Jiao S, et al. HIF-3α-Induced miR-630 expression promotes cancer hallmarks in cervical cancer cells by forming a positive feedback loop. Res Square  2021; 2021: 900566.
 [http://dx.doi.org/10.21203/rs.3.rs-900566/v1]

[84]
Jiang L, Shi S, Shi Q, Zhang H, Xia Y, Zhong T. MicroRNA-519d-3p inhibits proliferation and promotes apoptosis by targeting hif-2α in cervical cancer under hypoxic conditions. Oncol Res  2018; 26(7): 1055-62.
 [http://dx.doi.org/10.3727/096504018X15152056890500] [PMID: 29321085]

[85]
Yuan W, Xiaoyun H, Haifeng Q, et al. MicroRNA-218 enhances the radiosensitivity of human cervical cancer via promoting radiation induced apoptosis. Int J Med Sci  2014; 11(7): 691-6.
 [http://dx.doi.org/10.7150/ijms.8880] [PMID: 24843318]

[86]
Fakih MG. Metastatic colorectal cancer: Current state and future directions. J Clin Oncol  2015; 33(16): 1809-24.
 [http://dx.doi.org/10.1200/JCO.2014.59.7633] [PMID: 25918280]

[87]
Mármol I, Sánchez-de-Diego C, Pradilla Dieste A, Cerrada E, Rodriguez Yoldi M. Colorectal carcinoma: A general overview and future perspectives in colorectal cancer. Int J Mol Sci  2017; 18(1): 197.
 [http://dx.doi.org/10.3390/ijms18010197] [PMID: 28106826]

[88]
Kim CW, Oh ET, Kim JM, et al. Hypoxia-induced microRNA-590-5p promotes colorectal cancer progression by modulating matrix metalloproteinase activity. Cancer Lett  2018; 416: 31-41.
 [http://dx.doi.org/10.1016/j.canlet.2017.12.018] [PMID: 29247825]

[89]
Yang Y, Qu A, Wu Q, et al. Prognostic value of a hypoxia related microRNA signature in patients with colorectal cancer. Aging  2020; 12(1): 35-52.
 [http://dx.doi.org/10.18632/aging.102228] [PMID: 31926112]

[90]
Zichittella C, Barreca MM, Cordaro A, Corrado C, Alessandro R, Conigliaro A. Mir-675-5p supports hypoxia-induced drug resistance in colorectal cancer cells. BMC Cancer  2022; 22(1): 567.
 [http://dx.doi.org/10.1186/s12885-022-09666-2] [PMID: 35596172]

[91]
Nersisyan S, Galatenko A, Chekova M, Tonevitsky A. Hypoxia-induced miR-148a downregulation contributes to poor survival in colorectal cancer. Front Genet  2021; 12: 662468.
 [http://dx.doi.org/10.3389/fgene.2021.662468] [PMID: 34135940]

[92]
Long L, Huang G, Zhu H, Guo Y, Liu Y, Huo J. Down regulation of miR-138 promotes colorectal cancer metastasis via directly targeting TWIST2. J Transl Med  2013; 11(1): 275.
 [http://dx.doi.org/10.1186/1479-5876-11-275] [PMID: 24171926]

[93]
Nijhuis A, Thompson H, Adam J, et al. Remodelling of microRNAs in colorectal cancer by hypoxia alters metabolism profiles and 5-fluorouracil resistance. Hum Mol Genet  2017; 26(8): 1552-64.
 [http://dx.doi.org/10.1093/hmg/ddx059] [PMID: 28207045]

[94]
Hermann DM, Xin W, Bähr M, Giebel B, Doeppner TR. Emerging roles of extracellular vesicle-associated non coding RNAs in hypoxia: Insights from cancer, myocardial infarction and ischemic stroke. Theranostics  2022; 12(13): 5776-802.
 [http://dx.doi.org/10.7150/thno.73931] [PMID: 35966580]
Rights & Permissions Print Cite
Article Metrics
35
2
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/0115665240268661231128094831	Print ISSN 1566-5240
Publisher Name Bentham Science Publisher	Online ISSN 1875-5666
Current Molecular Medicine

Role of MicroRNA in Hypoxic Tumours and their Potential as Biomarkers for Early Detection of Cancer

Abstract

Molecular and Cellular Mechanisms in Vertigo / Vestibular Disorders

Current Molecular Medicine

Role of MicroRNA in Hypoxic Tumours and their Potential as Biomarkers for Early Detection of Cancer

Abstract

Call for Papers in Thematic Issues

Molecular and Cellular Mechanisms in Vertigo / Vestibular Disorders

Related Journals

Related Books

Related Articles
