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- 2018
miR-200b对三阴性乳腺癌细胞MDA-MB-231的负性调控作用
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Abstract:
摘要：目的 研究miRNA-200b对三阴性乳腺癌细胞增殖、侵袭能力的影响。方法 定量PCR检测人乳腺癌细胞株MCF-7、BT-474、MDA-MB-453、SKBR3、MDA-MB-468、MDA-MB-231中miRNA-200a/b/c的表达情况，通过miR-200b抑制剂及拟似物分别抑制、促进miR-200b的表达后，观察癌细胞增殖能力、克隆形成及侵袭能力的变化。结果 miRNA-200家族在Luminal型乳腺癌细胞MCF-7、BT-474和Her-2表达型MDA-MB-453、SKBR3的表达量高于三阴性型MDA-MB-468、MDA-MB-231的表达。通过inhibitor、mimics分别抑制、促进MDA-MB-231细胞中miR-200b的表达后，结果显示miR-200b对肿瘤细胞的增殖有抑制作用(P<0.05)，miRNA-200b组对肿瘤细胞的克隆形成有抑制作用(P<0.05)，对癌细胞侵袭有抑制作用(P<0.05)。结论 miRNA-200b对三阴性乳腺癌细胞MDA-MB-231具有负性调控作用，可以作为潜在的早期诊断及治疗靶点。
ABSTRACT: Objective To identify the regulation of miRNA-200b on proliferation of triple negative breast cancer cells. Methods The expressions of miRNA-200a/b/c in breast cancer cell lines MCF-7, BT-474, MDA-MB-453, SKBR3, MDA-MB-468, and MDA-MB-231 were detected by real-time PCR. MTT was used to detect MDA-MB-231 cell proliferation after miR-200b was downregulated and upregulated. The colony-forming efficiency of miR-200b was detected by colony forming assay. The transwell chamber was used to investigate the influence of miR-200b on invasion of MDA-MB-231 cells. Results miRNA-200a/b/c had relatively low expressions in triple negative breast cancer cell lines MDA-MB-468 and MDA-MB-231, but high expressions in luminal cells MCF-7, BT-474, and Her-2 positive cells MDA-MB-453, SKBR3. The upregulated miR-200b could suppress the proliferation, colony formation and cell invasion of MDA-MB-231 cells (P<0.05). Also the downregulated miR-200b promoted cell proliferation, colony forming and cell invasion (P<0.05). Conclusion miRNA-200b suppresses triple negative breast cancer cell MDA-MB-231, making it a potential biomarker and target for early diagnosis and therapy
| [1] | SIEGEL R L, MILLER K D, JEMAL A. Cancer Statistics, 2017[J]. CA Cancer J Clin, 2017, 67(1):7-30. |
| [2] | CRISCITIELLO C, AZIM HA, JR, SCHOUTEN PC, et al. Understanding the biology of triple-negative breast cancer[J]. Ann Oncol, 2012, 23(Suppl 6):vi13-18. |
| [3] | SHI L, ZHANG S, WU H, et al. MiR-200c increases theradiosensitivity of non-small-cell lung cancer cell line A549 by targeting VEGF-VEGFR2 pathway[J]. PLoS One, 2013, 8(10):e78344. |
| [4] | TUOMARILAM, LUOSTARI K, SOINI Y, et al.Overexpression of microRNA-200c predicts poor outcome in patients with PR-negative breast cancer[J]. PLoS One, 2014, 9(10):e109508. |
| [5] | MANAVALAN TT, TENG Y, LITCHFIELD LM, et al. Reduced expression of miR-200 family members contributes toantiestrogen resistance in LY2 human breast cancer cells[J]. PLoS One, 2013, 8(4):e62334. |
| [6] | D’IPPOLITO E, PLANTAMURA I, BONGIOVANNI L, et al. miR-9 and miR-200 regulatePDGFRbeta-mediated endothelial differentiation of tumor cells in triple-negative breast cancer[J]. Cancer Res, 2016, 76(18):5562-5572. |
| [7] | PERDIGAO-HENRIQUES R, PETROCCA F, ALTSCHULER G, et al. miR-200 promotes themesenchymal to epithelial transition by suppressing multiple members of the Zeb2 and Snail1 transcriptional repressor complexes[J]. Oncogene, 2016, 35(2):158-172. |
| [8] | CHOI SK, KIM HS, JIN T, et al. vOverexpression of the miR-141/200c cluster promotes the migratory and invasive ability of triple-negative breast cancer cells through the activation of the FAK and PI3K/AKT signaling pathways by secreting VEGF-A[J]. BMC Cancer, 2016, 16:570. |
| [9] | HUMPHRIES B, WANG Z, OOM AL, et al. MicroRNA-200b targets proteinkinase Calpha and suppresses triple-negative breast cancer metastasis[J]. Carcinogenesis, 2014, 35(10):2254-2263. |
| [10] | LIU T, ZHANG X, SHANG M, et al. Dysregulated expression of Slug, vimentin, and E-cadherin correlates with poor clinical outcome in patients with basal-like breast cancer[J]. J Surg Oncol, 2013, 107(2):188-194. |
| [11] | KORPAL M, ELL BJ, BUFFA FM, et al. Direct targeting of Sec23a by miR-200s influences cancer cellsecretome and promotes metastatic colonization[J]. Nat Med, 2011, 17(9):1101-1108. |
| [12] | 刘棣，黄辰，刁冬梅，等. miRNA-449家族靶向CCNE2对胃癌细胞生长的抑制调节作用[J]. 西安交通大学学报(医学版), 2012, 33(5):544-548. |
| [13] | BAYRAKTAR S, GLUCK S. Molecularly targeted therapies for metastatic triple-negative breast cancer[J]. Breast Cancer Res Treat, 2013, 138(1):21-35. |
| [14] | ANDRE F, ZIELINSKI CC. Optimal strategies for the treatment of metastatic triple-negative breast cancer with currently approved agents[J]. Ann Oncol, 2012, 23(Suppl 6):vi46-51. |
| [15] | GAO S L, WANG L Z, LIU H Y, et al. miR-200a inhibits tumor proliferation by targeting AP-2gamma inneuroblastoma cells[J]. Asian Pac J Cancer Prev, 2014, 15(11):4671-4676. |
