Obesity impacts the regulation of miR-10b and its targets in primary breast tumors
Abstract Background Obesity increases breast cancer (BC) risk in post-menopausal women by mostly unknown molecular mechanisms which may partly be regulated by microRNAs (miRNAs). Methods We isolated RNA from paired benign and malignant biopsies from 83 BC patients and determined miRNA profiles in sa...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-01-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12885-019-5300-6 |
| _version_ | 1829143875725295616 |
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| author | Ari Meerson Yaniv Eliraz Hila Yehuda Bridget Knight Malcolm Crundwell Douglas Ferguson Benjamin P. Lee Lorna W. Harries |
| author_facet | Ari Meerson Yaniv Eliraz Hila Yehuda Bridget Knight Malcolm Crundwell Douglas Ferguson Benjamin P. Lee Lorna W. Harries |
| author_sort | Ari Meerson |
| collection | DOAJ |
| description | Abstract Background Obesity increases breast cancer (BC) risk in post-menopausal women by mostly unknown molecular mechanisms which may partly be regulated by microRNAs (miRNAs). Methods We isolated RNA from paired benign and malignant biopsies from 83 BC patients and determined miRNA profiles in samples from 12 women at the extremes of the BMI distribution by RNA-seq. Candidates were validated in all samples. Associations between miR-10b expression and validated target transcript levels, and effects of targeted manipulation of miR-10b levels in a primary BC cell line on proliferation and invasion potential, were explored. Results Of the 148 miRNAs robustly expressed in breast tissues, the levels of miR-21, miR-10b, miR-451a, miR-30c, and miR-378d were significantly associated with presence of cancer. Of these, miR-10b showed a stronger down-regulation in the tumors of the obese subjects, as opposed to the lean. In ductal but not lobular tumors, significant inverse correlations were observed between the tumor levels of miR-10b and miR-30c and the mRNA levels of cancer-relevant target genes SRSF1, PIEZO1, MAPRE1, CDKN2A, TP-53 and TRA2B, as well as tumor grade. Suppression of miR-10b levels in BT-549 primary BC–derived cells increased cell proliferation and invasive capacity, while exogenous miR-10b mimic decreased invasion. Manipulation of miR-10b levels also inversely affected the mRNA levels of miR-10b targets BCL2L11, PIEZO1 and NCOR2. Conclusions Our findings suggest that miR-10b may be a mediator between obesity and cancer in post-menopausal women, regulating several known cancer-relevant genes. MiR-10b expression may have diagnostic and therapeutic implications for the incidence and prognosis of BC in obese women. |
| first_indexed | 2024-12-14T20:58:36Z |
| format | Article |
| id | doaj.art-f42bc0bfe938471bbb941b977d56bcea |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-14T20:58:36Z |
| publishDate | 2019-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-f42bc0bfe938471bbb941b977d56bcea2022-12-21T22:47:39ZengBMCBMC Cancer1471-24072019-01-0119111010.1186/s12885-019-5300-6Obesity impacts the regulation of miR-10b and its targets in primary breast tumorsAri Meerson0Yaniv Eliraz1Hila Yehuda2Bridget Knight3Malcolm Crundwell4Douglas Ferguson5Benjamin P. Lee6Lorna W. Harries7MIGAL - Galilee Research InstituteMIGAL - Galilee Research InstituteMIGAL - Galilee Research InstituteRoyal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter HospitalRoyal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter HospitalRoyal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter HospitalUniversity of Exeter Medical SchoolUniversity of Exeter Medical SchoolAbstract Background Obesity increases breast cancer (BC) risk in post-menopausal women by mostly unknown molecular mechanisms which may partly be regulated by microRNAs (miRNAs). Methods We isolated RNA from paired benign and malignant biopsies from 83 BC patients and determined miRNA profiles in samples from 12 women at the extremes of the BMI distribution by RNA-seq. Candidates were validated in all samples. Associations between miR-10b expression and validated target transcript levels, and effects of targeted manipulation of miR-10b levels in a primary BC cell line on proliferation and invasion potential, were explored. Results Of the 148 miRNAs robustly expressed in breast tissues, the levels of miR-21, miR-10b, miR-451a, miR-30c, and miR-378d were significantly associated with presence of cancer. Of these, miR-10b showed a stronger down-regulation in the tumors of the obese subjects, as opposed to the lean. In ductal but not lobular tumors, significant inverse correlations were observed between the tumor levels of miR-10b and miR-30c and the mRNA levels of cancer-relevant target genes SRSF1, PIEZO1, MAPRE1, CDKN2A, TP-53 and TRA2B, as well as tumor grade. Suppression of miR-10b levels in BT-549 primary BC–derived cells increased cell proliferation and invasive capacity, while exogenous miR-10b mimic decreased invasion. Manipulation of miR-10b levels also inversely affected the mRNA levels of miR-10b targets BCL2L11, PIEZO1 and NCOR2. Conclusions Our findings suggest that miR-10b may be a mediator between obesity and cancer in post-menopausal women, regulating several known cancer-relevant genes. MiR-10b expression may have diagnostic and therapeutic implications for the incidence and prognosis of BC in obese women.http://link.springer.com/article/10.1186/s12885-019-5300-6miR-10bBreast cancerObesitymicroRNATumor suppressorsOncogenes |
| spellingShingle | Ari Meerson Yaniv Eliraz Hila Yehuda Bridget Knight Malcolm Crundwell Douglas Ferguson Benjamin P. Lee Lorna W. Harries Obesity impacts the regulation of miR-10b and its targets in primary breast tumors BMC Cancer miR-10b Breast cancer Obesity microRNA Tumor suppressors Oncogenes |
| title | Obesity impacts the regulation of miR-10b and its targets in primary breast tumors |
| title_full | Obesity impacts the regulation of miR-10b and its targets in primary breast tumors |
| title_fullStr | Obesity impacts the regulation of miR-10b and its targets in primary breast tumors |
| title_full_unstemmed | Obesity impacts the regulation of miR-10b and its targets in primary breast tumors |
| title_short | Obesity impacts the regulation of miR-10b and its targets in primary breast tumors |
| title_sort | obesity impacts the regulation of mir 10b and its targets in primary breast tumors |
| topic | miR-10b Breast cancer Obesity microRNA Tumor suppressors Oncogenes |
| url | http://link.springer.com/article/10.1186/s12885-019-5300-6 |
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