Remodelling of microRNAs in colorectal cancer by hypoxia alters metabolism profiles and 5-fluorouracil resistance
Solid tumours have oxygen gradients and areas of near and almost total anoxia. Hypoxia reduces sensitivity to 5-fluorouracil (5-FU)-chemotherapy for colorectal cancer (CRC). MicroRNAs (miRNAs) are hypoxia sensors and were altered consistently in six CRC cell lines (colon cancer: DLD-1, HCT116 and HT...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Oxford University Press
2017
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| _version_ | 1826277705411198976 |
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| author | Nijhuis, A Thompson, H Adam, J Parker, A Gammon, L Lewis, A Bundy, J Soga, T Jalaly, A Propper, D Jeffery, R Suraweera, N McDonald, S Thaha, M Feakins, R Lowe, R Bishop, C Silver, A |
| author_facet | Nijhuis, A Thompson, H Adam, J Parker, A Gammon, L Lewis, A Bundy, J Soga, T Jalaly, A Propper, D Jeffery, R Suraweera, N McDonald, S Thaha, M Feakins, R Lowe, R Bishop, C Silver, A |
| author_sort | Nijhuis, A |
| collection | OXFORD |
| description | Solid tumours have oxygen gradients and areas of near and almost total anoxia. Hypoxia reduces sensitivity to 5-fluorouracil (5-FU)-chemotherapy for colorectal cancer (CRC). MicroRNAs (miRNAs) are hypoxia sensors and were altered consistently in six CRC cell lines (colon cancer: DLD-1, HCT116 and HT29; rectal cancer: HT55, SW837 and VACO4S) maintained in hypoxia (1 and 0.2% oxygen) compared with normoxia (20.9%). CRC cell lines also showed altered amino acid metabolism in hypoxia and hypoxia-responsive miRNAs were predicted to target genes in four metabolism pathways: beta-alanine; valine, leucine, iso-leucine; aminoacyl-tRNA; and alanine, aspartate, glutamate. MiR-210 was increased in hypoxic areas of CRC tissues and hypoxia-responsive miR-21 and miR-30d, but not miR-210, were significantly increased in 5-FU resistant CRCs. Treatment with miR-21 and miR-30d antagonists sensitized hypoxic CRC cells to 5-FU. Our data highlight the complexity and tumour heterogeneity caused by hypoxia. MiR-210 as a hypoxic biomarker, and the targeting of miR-21 and miR-30d and/or the amino acid metabolism pathways may offer translational opportunities. |
| first_indexed | 2024-03-06T23:32:56Z |
| format | Journal article |
| id | oxford-uuid:6caeb38e-02bd-41f5-beba-ed00e1f5f20a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:32:56Z |
| publishDate | 2017 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:6caeb38e-02bd-41f5-beba-ed00e1f5f20a2022-03-26T19:12:42ZRemodelling of microRNAs in colorectal cancer by hypoxia alters metabolism profiles and 5-fluorouracil resistanceJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6caeb38e-02bd-41f5-beba-ed00e1f5f20aEnglishSymplectic Elements at OxfordOxford University Press2017Nijhuis, AThompson, HAdam, JParker, AGammon, LLewis, ABundy, JSoga, TJalaly, APropper, DJeffery, RSuraweera, NMcDonald, SThaha, MFeakins, RLowe, RBishop, CSilver, ASolid tumours have oxygen gradients and areas of near and almost total anoxia. Hypoxia reduces sensitivity to 5-fluorouracil (5-FU)-chemotherapy for colorectal cancer (CRC). MicroRNAs (miRNAs) are hypoxia sensors and were altered consistently in six CRC cell lines (colon cancer: DLD-1, HCT116 and HT29; rectal cancer: HT55, SW837 and VACO4S) maintained in hypoxia (1 and 0.2% oxygen) compared with normoxia (20.9%). CRC cell lines also showed altered amino acid metabolism in hypoxia and hypoxia-responsive miRNAs were predicted to target genes in four metabolism pathways: beta-alanine; valine, leucine, iso-leucine; aminoacyl-tRNA; and alanine, aspartate, glutamate. MiR-210 was increased in hypoxic areas of CRC tissues and hypoxia-responsive miR-21 and miR-30d, but not miR-210, were significantly increased in 5-FU resistant CRCs. Treatment with miR-21 and miR-30d antagonists sensitized hypoxic CRC cells to 5-FU. Our data highlight the complexity and tumour heterogeneity caused by hypoxia. MiR-210 as a hypoxic biomarker, and the targeting of miR-21 and miR-30d and/or the amino acid metabolism pathways may offer translational opportunities. |
| spellingShingle | Nijhuis, A Thompson, H Adam, J Parker, A Gammon, L Lewis, A Bundy, J Soga, T Jalaly, A Propper, D Jeffery, R Suraweera, N McDonald, S Thaha, M Feakins, R Lowe, R Bishop, C Silver, A Remodelling of microRNAs in colorectal cancer by hypoxia alters metabolism profiles and 5-fluorouracil resistance |
| title | Remodelling of microRNAs in colorectal cancer by hypoxia alters metabolism profiles and 5-fluorouracil resistance |
| title_full | Remodelling of microRNAs in colorectal cancer by hypoxia alters metabolism profiles and 5-fluorouracil resistance |
| title_fullStr | Remodelling of microRNAs in colorectal cancer by hypoxia alters metabolism profiles and 5-fluorouracil resistance |
| title_full_unstemmed | Remodelling of microRNAs in colorectal cancer by hypoxia alters metabolism profiles and 5-fluorouracil resistance |
| title_short | Remodelling of microRNAs in colorectal cancer by hypoxia alters metabolism profiles and 5-fluorouracil resistance |
| title_sort | remodelling of micrornas in colorectal cancer by hypoxia alters metabolism profiles and 5 fluorouracil resistance |
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