MiR-382 inhibits proliferation and migration of triple negative breast cancer cell line 4T1 by mediating PGC-1α

Youyang LEI; Hua ZHOU; Meng DAI; Xin JIN; Jia MING

doi:10.16016/j.1000-5404.201903048

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MiR-382 inhibits proliferation and migration of triple negative breast cancer cell line 4T1 by mediating PGC-1α

更新时间：2026-01-09

- MiR-382 inhibits proliferation and migration of triple negative breast cancer cell line 4T1 by mediating PGC-1α
- Journal of Third Military Medical University Vol. 41, Issue 15, Pages: 1415-1422(2019)
- 作者机构：
- 作者简介：
- 基金信息：
  
  the Medical Research Project of Chongqing Municipal Health and Family Planning Commission(2016ZDXM012);the Technology Innovation and Application Pilot Project of Chongqing Municipal Science and Technology Committee(社会民生类，CSTC2018jscx-msybx0020);the Project of Science and Technology Plan of Yuzhong District, Chongqing(20160104)
- DOI：10.16016/j.1000-5404.201903048
  CLC：
- Received：06 March 2019，
  
  Published：15 August 2019
- 稿件说明：
移动端阅览
Youyang LEI, Hua ZHOU, Meng DAI, et al. MiR-382 inhibits proliferation and migration of triple negative breast cancer cell line 4T1 by mediating PGC-1α[J]. Journal of Third Military Medical University, 2019, 41(15): 1415-1422.
DOI：

Youyang LEI, Hua ZHOU, Meng DAI, et al. MiR-382 inhibits proliferation and migration of triple negative breast cancer cell line 4T1 by mediating PGC-1α[J]. Journal of Third Military Medical University, 2019, 41(15): 1415-1422. DOI： 10.16016/j.1000-5404.201903048.

摘要

Abstract

Objective

To explore the effect of miR-382 down-regulating PGC-1α on the biological behaviors of triple negative breast cancer 4T1 cells.

Methods

① After miR-382 mimics or inhibitory probe anti-miR-382 was transfected into 4T1 cells

the expression level of miR-382 was detected by qRT-PCR. The changes of PGC-1α expression at mRNA and protein levels were detected by qRT-PCR and Western blotting

respectively. ② Luciferase reporter gene assay was adopted to identify the binding site of miR-382 mimics to PGC-1α 3'UTR. ③miR-382 mimics or control miR were co-transfected into 4T1 cells with pCDNA3.1 or pCDNA-PGC1α

respectively. Transwell migration assay

CCK8 assay and subcutaneous xenografts and tail vein lung xenografts were respectively used to detect the changes in cell invasiveness

cell proliferation

and tumor growth and lung metastasis in mice.

Results

The expression of PGC-1α was significantly decreased in 4T1 cells afte

r transfection with miR-382 mimics (

0.05)

and it was obviously increased after transfection with anti-miR-382 (

0.05). There was a targeted regulatory core sequence (ACAACTT) of miR-382 and PGC-1α

and the site was at PGC-1α 3'UTR 565-582. Compared with the control +pCDNA3.1 group

the cell migration and proliferation activity of the miR-382+pCDNA3.1 group was significantly decreased

and the size of the 4T1 subcutaneous tumor and the area of metastatic tumor in the lung were notably decreased (

0.05). Compared with the control +pCDNA3.1 group

the cell migration and proliferation activity were significantly increased in the miR-382+pCDNA-PGC-1α group

and the size of 4T1 subcutaneous tumor and the area of metastatic tumor in the lung was significantly increased (

0.05); The antitumor effect of miR-382 was blocked by overexpression of PGC-1α.

Conclusion

MiR-382 inhibits the proliferation and lung metastasis of 4T1 cells by down-regulating PGC-1α

and the interaction site may be PGC-1α 3'UTR 565-582.

关键词

Keywords

references

BOSCH A EROLES P ZARAGOZA R Triple-negative breast cancer:molecular features, pathogenesis, treatment and current lines of research Cancer Treatment Rev 2010 36 3 206 215 10.1016/j.ctrv.2009.12.002 BOSCH A, EROLES P, ZARAGOZA R, et al .Triple-negative breast cancer:molecular features, pathogenesis, treatment and current lines of research.[J ] .Cancer Treatment Rev, 2010, 36(3):206-215.

LEBLEU V S O'CONNELL J T GONZALEZ HERRERA K N PGC-1α mediates mitochondrial biogenesis and oxidative phosphorylation in cancer cells to promote metastasis Nat Cell Biol 2014 16 10 992 1003 10.1038/ncb3039 LEBLEU V S, O'CO NNELL J T, GONZALEZ HERRERA K N, et al .PGC-1α mediates mitochondrial biogenesis and oxidative phosphorylation in cancer cells to promote metastasis[J ] .Nat Cell Biol, 2014, 16(10):992-1003.DOI:10.1038/ncb3039.

PUIGSERVER P WU Z PARK C W A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis Cell 1998 92 6 829 839 10.1016/S0092-8674(00)81410-5 PUIGSERVER P, WU Z, PARK C W, et al .A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis[J ] .Cell, 1998, 92(6):829-839.DOI:10.1016/S0092-8674(00)81410-5.

CALIN G A CROCE C M MicroRNA signatures in human cancers Nat Rev Cancer 2006 6 11 857 866 10.1038/nrc1997 CALIN G A, CROCE C M.MicroRNA signatures in human cancers[J].Nat Rev Cancer, 2006, 6(11):857-866.DOI:10.1038/nrc1997.

FU L LI Z ZHU J Serum expression levels of microRNA-382-3p, -598-3p, -1246 and-184 in breast cancer patients Oncol Letters 2016 12 1 269 10.3892/ol.2016.4582 FU L, LI Z, ZHU J, et al .Serum expression levels of microRNA-382-3p, -598-3p, -1246 and-184 in breast cancer patients.[J ] .Oncol Letters, 2016, 12(1):269.DOI:10.3892/ol.2016.4582.

代朦靳鑫雷优扬过表达miR-382的肿瘤相关巨噬细胞对三阴性乳腺癌生物学特性的影响第三军医大学学报 2018 40 15 1375 1382 10.16016/j.1000-5404.201801107 http://aammt.tmmu.edu.cn/oa/DArticle.aspx?type=view&id=201801107 代朦, 靳鑫, 雷优扬, 等.过表达miR-382的肿瘤相关巨噬细胞对三阴性乳腺癌生物学特性的影响[J].第三军医大学学报, 2018, 40(15):1375-1382.DOI:10.16016/j.1000-5404.201801107.

DAI M JIN X LEI Y Y Effect of miR-382 overexpressing tumor-associated macrophages on biological properties of triple-negative breast cancer 4T1 cells J Third Mil Med Univ 2018 40 15 1375 1382 10.16016/j.1000-5404.201801107 http://aammt.tmmu.edu.cn/oa/DArticle.aspx?type=view&id=201801107 DAI M, JIN X, LEI Y Y, et al .Effect of miR-382 overexpressing tumor-associated macrophages on biological properties of triple-negative breast cancer 4T1 cells[J ] .J Third Mil Med Univ, 2018, 40(15):1375-1382.DOI:10.16016/j.1000-5404.201801107.

靳鑫倪田根王宁 PGC-1α通过线粒体介导巨噬细胞极化状态的机制研究第三军医大学学报 2019 41 1 56 62 10.16016/j.1000-5404.201808139 http://aammt.tmmu.edu.cn/oa/DArticle.aspx?type=view&id=201808139 靳鑫, 倪田根, 王宁, 等.PGC-1α通过线粒体介导巨噬细胞极化状态的机制研究[J].第三军医大学学报, 2019, 41(1):56-62.DOI:10.16016/j.1000-5404.201808139.

JIN X NI T G WANG N Mechanism of mitochondria-mediated PGC-1α in macrophage polarization J Third Mil Med Univ 2019 41 01 56 62 10.16016/j.1000-5404.201808139 http://aammt.tmmu.edu.cn/oa/DArticle.aspx?type=view&id=201808139 JIN X, NI T G, WANG N, et al .Mechanism of mitochondria-mediated PGC-1α in macrophage polarization[J ] .J Third Mil Med Univ, 2019, 41(01):56-62.DOI:10.16016/j.1000-5404.201808139.

FAN L STRASSER-WEIPPL K LI J J Breast cancer in China Lancet Oncology 2014 15 7 e279 e289 10.1016/S1470-2045(13)70567-9 FAN L, STRASSER-WEIPPL K, LI J J, et al .Breast cancer in China[J ] .Lancet Oncology, 2014, 15(7):e279-e289.DOI:10.1016/S1470-2045(13)70567-9.

COSTA R SHAH A N SANTA-MARIA C A Targeting Epidermal Growth Factor Receptor in triple negative breast cancer:New discoveries and practical insights for drug development Cancer Treatment Rev 2017 53 111 119 10.1016/j.ctrv.2016.12.010 COSTA R, SHAH A N, SANTA-MARIA C A, et al .Targeting Epidermal Growth Factor Receptor in triple negative breast cancer:New discoveries and practical insights for drug development[J ] .Cancer Treatment Rev, 2017, 53:111-119.DOI:10.1016/j.ctrv.2016.12.010.

DENKERT C LIEDTKE C TUTT A Molecular alterations in triple-negative breast cancer-the road to new treatment strategies Lancet 2017 389 10087 2430 2442 10.1016/S0140-6736(16)32454-0 DENKERT C, LIEDTKE C, TUTT A, et al .Molecular alterations in triple-negative breast cancer-the road to new treatment strategies[J ] .Lancet, 2017, 389(10087):2430-2442.DOI:10.1016/S0140-6736(16)32454-0.

LEBLEU V S O'CONNELL J T GONZALEZ HERRERA K N PGC-1α mediates mitochondrial biogenesis and oxidative phosphorylation in cancer cells to promote metastasis Nat Cell Biol 2014 16 10 992 1003 10.1038/ncb3039 LEBLEU V S, O'CONNELL J T, GONZALEZ HERRERA K N, et al .PGC-1α mediates mitochondrial biogenesis and oxidative phosphorylation in cancer cells to promote metastasis[J ] .Nat Cell Biol, 2014, 16(10):992-1003.DOI:10.1038/ncb3039.

ST-PIERRE J DRORI S ULDRY M Suppression of reactive oxygen species and neurodegeneration by the PGC-1α transcriptional coactivators Cell 2006 127 2 397 408 10.1016/j.cell.2006.09.024 ST-PIERRE J, DRORI S, ULDRY M, et al .Suppression of reactive oxygen species and neurodegeneration by the PGC-1α transcriptional coactivators[J ] .Cell, 2006, 127(2 ):397-408.DOI:10.1016/j.cell.2006.09.024.

YU Z BASERGA R CHEN L MicroRNA, cell cycle, and human breast cancer Am J Pathol 2010 176 3 1058 1064 10.2353/ajpath.2010.090664 YU Z, BASERGA R, CHEN L, et al .MicroRNA, cell cycle, and human breast cancer[J ] .Am J Pathol, 2010, 176(3):1058-1064.DOI:10.2353/ajpath.2010.090664.

STENVANG J PETRI A LINDOW M Inhibition of microRNA function by antimiR oligonucleotides Silence 2012 3 1 1 10.1186/1758-907X-3-1 STENVANG J, PETRI A, LINDOW M, et al .Inhibition of microRNA function by antimiR oligonucleotides[J ] .Silence, 2012, 3(1):1.DOI:10.1186/1758-907X-3-1.

ZHANG H LI Y LAI M The microRNA network and tumor metastasis Oncogene 2010 29 937 948 10.1038/onc.2009.406 ZHANG H, LI Y, LAI M.The microRNA network and tumor metastasis.Oncogene, 2010, 29:937-948.DOI:10.1038/onc.2009.406.

JOVANOVIC M HENGARTNER M O miRNAs and apoptosis:RNAs to die for Oncogene 2006 25 6176 6187 10.1038/sj.onc.1209912 JOVANOVIC M, HENGARTNER M O.miRNAs and apoptosis:RNAs to die for.Oncogene, 2006, 25:6176-6187.DOI:10.1038/sj.onc.1209912.

LI Y HONG F YU Z Decreased expression of microRNA-206 in breast cancer and its association with disease characteristics and patient survival J Int Med Res 2013 41 3 596 602 10.1177/0300060513485856 LI Y, HONG F, YU Z.Decreased expression of microRNA-206 in breast cancer and its association with disease characteristics and patient survival[J].J Int Med Res, 2013, 41(3):596-602.DOI:10.1177/0300060513485856.

KONG Y W FERLAND-MCCOLLOUGH D JACKSON T J MicroRNAs in cancer management Lancet Oncol 2012 13 6 e249 e258 10.1016/S1470-2045(12)70073-6 KONG Y W, FERLAND-MCCOLLOUGH D, JACKSON T J, et al .MicroRNAs in cancer management[J ] .Lancet Oncol.2012, 13(6):e249-e258.DOI:10.1016/S1470-2045(12)70073-6.

CHEN T REN H THAKUR A MiR-382 inhibits tumor progression by targeting SETD8 in non-small cell lung cancer Biomedicine&Pharmacotherapy 2017 86 248 253 10.1016/j.biopha.2016.12.007 CHEN T, REN H, THAKUR A, et al .MiR-382 inhibits tumor progression by targeting SETD8 in non-small cell lung cancer[J ] .Biomedicine & Pharmacotherapy, 2017, 86:248-253.DOI:10.1016/j.biopha.2016.12.007.

ZHOU B SONG J HAN T MiR-382 inhibits cell growth and invasion by targeting NR2F2 in colorectal cancer Mol Carcinogen 2016 55 12 2260 2267 10.1002/mc.22466 ZHOU B, SONG J, HAN T, et al .MiR-382 inhibits cell growth and invasion by targeting NR2F2 in colorectal cancer[J ] .Mol Carcinogen, 2016, 55(12):2260-2267.DOI:10.1002/mc.22466.

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