MicroRNA-503 inhibits the proliferation and invasion of breast cancer cells via targeting insulin-like growth factor 1 receptor Retraction in /10.3892/mmr.2022.12651

Yan,Jingwang; Xu,Yonghuan; Wang,Haipeng; Du,Taiping; Chen,Hao

doi:10.3892/mmr.2017.6816

MicroRNA-503 inhibits the proliferation and invasion of breast cancer cells via targeting insulin-like growth factor 1 receptor

Retraction in: /10.3892/mmr.2022.12651

Authors:
- Jingwang Yan
- Yonghuan Xu
- Haipeng Wang
- Taiping Du
- Hao Chen
View Affiliations

Affiliations: Department of General Surgery, Xinxiang Center Hospital, Xinxiang, Henan 453000, P.R. China, Department of Oncology, People's Hospital of Xixia County, Nanyang, Henan 474550, P.R. China
Published online on: June 20, 2017 https://doi.org/10.3892/mmr.2017.6816
Pages: 1707-1714
Copyright: © Yan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

MicroRNAs (miRs), a class of non-coding RNAs that are 18‑25 nucleotides in length, serve as key regulators in the development and progression of human cancers. Previously, miR‑503 has been implicated in breast cancer. However, the underlying mechanism of miR‑503 in regulating the proliferation and invasion of breast cancer cells remains largely unknown. In the present study, reverse transcription‑quantitative polymerase chain reaction analysis indicated that the expression of miR‑503 was significantly reduced in breast cancer tissues compared with their matched adjacent normal tissues. Furthermore, miR‑503 expression levels were markedly reduced in T2‑T4 stage breast cancer, compared with T1 stage. Insulin‑like growth factor 1 receptor (IGF‑1R) was further identified as a novel target of miR‑503. Overexpression of miR‑503 significantly suppressed the protein expression levels of IGF‑1R. Furthermore, it inhibited the proliferation and invasion of human breast cancer MCF‑7 cells, as assessed by MTT and Transwell assays, respectively. However, restoration of IGF‑1R expression markedly ameliorated the suppressive effects of miR‑503 overexpression on MCF‑7 cell proliferation and invasion, indicating that miR‑503 inhibits breast cancer cell proliferation and invasion at least partially via directly targeting IGF‑1R. Furthermore, the mRNA and protein expression levels of IGF‑1R were demonstrated to be significantly increased in breast cancer tissues compared with their matched adjacent normal tissues. In addition, IGF‑1R mRNA expression levels were reversely correlated with miR‑503 expression levels in breast tumors, suggesting that the upregulation of IGF‑1R may be due to downregulation of miR‑503 in breast cancer. In conclusion, the present study expanded the understanding of the regulatory mechanism of miR‑503 in breast cancer, and implicates the miR‑503/IGF‑1R axis as a potential therapeutic target for breast cancer.

View Figures

View References

1	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
2	DeSantis C, Ma J, Bryan L and Jemal A: Breast cancer statistics, 2013. CA Cancer J Clin. 64:52–62. 2014. View Article : Google Scholar : PubMed/NCBI
3	Munagala R, Aqil F, Vadhanam MV and Gupta RC: MicroRNA ‘signature’ during estrogen-mediated mammary carcinogenesis and its reversal by ellagic acid intervention. Cancer Lett. 339:175–184. 2013. View Article : Google Scholar : PubMed/NCBI
4	Shin VY, Siu JM, Cheuk I, Ng EK and Kwong A: Circulating cell-free miRNAs as biomarker for triple-negative breast cancer. Br J Cancer. 112:1751–1759. 2015. View Article : Google Scholar : PubMed/NCBI
5	Negrini M and Calin GA: Breast cancer metastasis: A microRNA story. Breast Cancer Res. 10:2032008. View Article : Google Scholar : PubMed/NCBI
6	John B, Enright AJ, Aravin A, Tuschl T, Sander C and Marks DS: Human MicroRNA targets. PLoS Biol. 2:e3632004. View Article : Google Scholar : PubMed/NCBI
7	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
8	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
9	Lerebours F, Cizeron-Clairac G, Susini A, Vacher S, Mouret-Fourme E, Belichard C, Brain E, Alberini JL, Spyratos F, Lidereau R and Bieche I: miRNA expression profiling of inflammatory breast cancer identifies a 5-miRNA signature predictive of breast tumor aggressiveness. Int J Cancer. 133:1614–1623. 2013. View Article : Google Scholar : PubMed/NCBI
10	Long J, Ou C, Xia H, Zhu Y and Liu D: MiR-503 inhibited cell proliferation of human breast cancer cells by suppressing CCND1 expression. Tumour Biol. 36:8697–8702. 2015. View Article : Google Scholar : PubMed/NCBI
11	Polioudakis D, Abell NS and Iyer VR: miR-503 represses human cell proliferation and directly targets the oncogene DDHD2 by non-canonical target pairing. BMC Genomics. 16:402015. View Article : Google Scholar : PubMed/NCBI
12	King H, Aleksic T, Haluska P and Macaulay VM: Can we unlock the potential of IGF-1R inhibition in cancer therapy? Cancer Treat Rev. 40:1096–1105. 2014. View Article : Google Scholar : PubMed/NCBI
13	Crudden C, Girnita A and Girnita L: Targeting the IGF-1R: The tale of the tortoise and the hare. Front Endocrinol (Lausanne). 6:642015.PubMed/NCBI
14	Singh P, Alex JM and Bast F: Insulin receptor (IR) and insulin-like growth factor receptor 1 (IGF-1R) signaling systems: Novel treatment strategies for cancer. Med Oncol. 31:8052014. View Article : Google Scholar : PubMed/NCBI
15	Dricu A, Kanter L, Wang M, Nilsson G, Hjertman M, Wejde J and Larsson O: Expression of the insulin-like growth factor 1 receptor (IGF-1R) in breast cancer cells: Evidence for a regulatory role of dolichyl phosphate in the transition from an intracellular to an extracellular IGF-1 pathway. Glycobiology. 9:571–579. 1999. View Article : Google Scholar : PubMed/NCBI
16	Al Sarakbi W, Chong YM, Williams SL, Sharma AK and Mokbel K: The mRNA expression of IGF-1 and IGF-1R in human breast cancer: Association with clinico-pathological parameters. J Carcinog. 5:162006. View Article : Google Scholar : PubMed/NCBI
17	Kucab JE and Dunn SE: Role of IGF-1R in mediating breast cancer invasion and metastasis. Breast Dis. 17:41–47. 2003. View Article : Google Scholar : PubMed/NCBI
18	Hou X, Huang F, Macedo LF, Harrington SC, Reeves KA, Greer A, Finckenstein FG, Brodie A, Gottardis MM, Carboni JM and Haluska P: Dual IGF-1R/InsR inhibitor BMS-754807 synergizes with hormonal agents in treatment of estrogen-dependent breast cancer. Cancer Res. 71:7597–7607. 2011. View Article : Google Scholar : PubMed/NCBI
19	Chen Y, Zhu C, Peng Z, Dai Y and Gu Y: Lentivirus-mediated short-hairpin RNA targeting IGF-1R inhibits growth and lymphangiogenesis in breast cancer. Oncol Rep. 28:1778–1784. 2012.PubMed/NCBI
20	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
21	Wang K, Jia Z, Zou J, Zhang A, Wang G, Hao J, Wang Y, Yang S and Pu P: Analysis of hsa-miR-30a-5p expression in human gliomas. Pathol Oncol Res. 19:405–411. 2013. View Article : Google Scholar : PubMed/NCBI
22	Kimura S, Naganuma S, Susuki D, Hirono Y, Yamaguchi A, Fujieda S, Sano K and Itoh H: Expression of microRNAs in squamous cell carcinoma of human head and neck and the esophagus: miR-205 and miR-21 are specific markers for HNSCC and ESCC. Oncol Rep. 23:1625–1633. 2010.PubMed/NCBI
23	Visone R, Pallante P, Vecchione A, Cirombella R, Ferracin M, Ferraro A, Volinia S, Coluzzi S, Leone V, Borbone E, et al: Specific microRNAs are downregulated in human thyroid anaplastic carcinomas. Oncogene. 26:7590–7595. 2007. View Article : Google Scholar : PubMed/NCBI
24	Zhu J, Zeng Y, Xu C, Qin H, Lei Z, Shen D, Liu Z and Huang JA: Expression profile analysis of microRNAs and downregulated miR-486-5p and miR-30a-5p in non-small cell lung cancer. Oncol Rep. 34:1779–1786. 2015.PubMed/NCBI
25	Jia Z, Wang K, Wang G, Zhang A and Pu P: MiR-30a-5p antisense oligonucleotide suppresses glioma cell growth by targeting SEPT7. PLoS One. 8:e550082013. View Article : Google Scholar : PubMed/NCBI
26	Wang X, Wang K, Han L, Zhang A, Shi Z, Zhang K, Zhang H, Yang S, Pu P, Shen C, et al: PRDM1 is directly targeted by miR-30a-5p and modulates the Wnt/β-catenin pathway in a Dkk1-dependent manner during glioma growth. Cancer Lett. 331:211–219. 2013. View Article : Google Scholar : PubMed/NCBI
27	Dai H, Kang B, Zuo D and Zuo G: Effect of miR-30a-5p on the proliferation, apoptosis, invasion and migration of SMCC-7721 human hepatocellular carcinoma cells. Zhonghua Gan Zang Bing Za Zhi. 22:915–920. 2014.(In Chinese). PubMed/NCBI
28	Baraniskin A, Birkenkamp-Demtroder K, Maghnouj A, Zöllner H, Munding J, Klein-Scory S, Reinacher-Schick A, Schwarte-Waldhoff I, Schmiegel W and Hahn SA: MiR-30a-5p suppresses tumor growth in colon carcinoma by targeting DTL. Carcinogenesis. 33:732–739. 2012. View Article : Google Scholar : PubMed/NCBI
29	Ruiz-Llorente L, Ardila-González S, Fanjul LF, Martinez-Iglesias O and Aranda A: microRNAs 424 and 503 are mediators of the anti-proliferative and anti-invasive action of the thyroid hormone receptor beta. Oncotarget. 5:2918–2933. 2014. View Article : Google Scholar : PubMed/NCBI
30	Chen J, Duan Y, Zhang X, Ye Y, Ge B and Chen J: Genistein induces apoptosis by the inactivation of the IGF-1R/p-Akt signaling pathway in MCF-7 human breast cancer cells. Food Funct. 6:995–1000. 2015. View Article : Google Scholar : PubMed/NCBI
31	Heskamp S, Boerman OC, Molkenboer-Kuenen JD, Wauters CA, Strobbe LJ, Mandigers CM, Bult P, Oyen WJ, van der Graaf WT and van Laarhoven HW: Upregulation of IGF-1R expression during neoadjuvant therapy predicts poor outcome in breast cancer patients. PLoS One. 10:e01177452015. View Article : Google Scholar : PubMed/NCBI