Long non‑coding RNA DANCR aggravates breast cancer through the miR‑34c/E2F1 feedback loop

Yan,Shuai; Yan,Shuai; Teng,Lizhi; Teng,Lizhi; Du,Juntong; Du,Juntong; Ji,Liang; Ji,Liang; Xu,Peng; Xu,Peng; Zhao,Wenxi; Zhao,Wenxi; Tao,Weiyang; Tao,Weiyang

doi:10.3892/mmr.2024.13217

Long non‑coding RNA DANCR aggravates breast cancer through the miR‑34c/E2F1 feedback loop

Authors:
- Shuai Yan
- Lizhi Teng
- Juntong Du
- Liang Ji
- Peng Xu
- Wenxi Zhao
- Weiyang Tao
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Affiliations: Department of Breast Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China
Published online on: April 5, 2024 https://doi.org/10.3892/mmr.2024.13217
Article Number: 93
Copyright: © Yan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Emerging scientific evidence has suggested that the long non‑coding (lnc)RNA differentiation antagonizing non‑protein coding RNA (DANCR) serves a significant role in human tumorigenesis and cancer progression; however, the precise mechanism of its function in breast cancer remains to be fully understood. Therefore, the objective of the present study was to manipulate DANCR expression in MCF7 and MDA‑MB‑231 cells using lentiviral vectors to knock down or overexpress DANCR. This manipulation, alongside the analysis of bioinformatics data, was performed to investigate the potential mechanism underlying the role of DANCR in cancer. The mRNA and/or protein expression levels of DANCR, miR‑34c‑5p and E2F transcription factor 1 (E2F1) were assessed using reverse transcription‑quantitative PCR and western blotting, respectively. The interactions between these molecules were validated using chromatin immunoprecipitation and dual‑luciferase reporter assays. Additionally, fluorescence in situ hybridization was used to confirm the subcellular localization of DANCR. Cell proliferation, migration and invasion were determined using 5‑ethynyl‑2'‑deoxyuridine, wound healing and Transwell assays, respectively. The results of the present study demonstrated that DANCR had a regulatory role as a competing endogenous RNA and upregulated the expression of E2F1 by sequestering miR‑34c‑5p in breast cancer cells. Furthermore, E2F1 promoted DANCR transcription by binding to its promoter in breast cancer cells. Notably, the DANCR/miR‑34c‑5p/E2F1 feedback loop enhanced cell proliferation, migration and invasion in breast cancer cells. Thus, these findings suggested that targeting DANCR may potentially provide a promising future therapeutic strategy for breast cancer treatment.

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1	Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71:209–249. 2021. View Article : Google Scholar : PubMed/NCBI
2	Ramamoorthi G, Kodumudi K, Gallen C, Zachariah NN, Basu A, Albert G, Beyer A, Snyder C, Wiener D, Costa RLB and Czerniecki BJ: Disseminated cancer cells in breast cancer: Mechanism of dissemination and dormancy and emerging insights on therapeutic opportunities. Semin Cancer Biol. 78:78–89. 2022. View Article : Google Scholar : PubMed/NCBI
3	Zhu L, Jiang S, Yu S, Liu X, Pu S, Xie P, Chen H, Liao X, Wang K and Wang B: Increased SIX-1 expression promotes breast cancer metastasis by regulating lncATB-miR-200s-ZEB1 axis. J Cell Mol Med. 24:5290–5303. 2020. View Article : Google Scholar : PubMed/NCBI
4	Zhu L, Tian Q, Gao H, Wu K, Wang B, Ge G, Jiang S, Wang K, Zhou C, He J, et al: PROX1 promotes breast cancer invasion and metastasis through WNT/β-catenin pathway via interacting with hnRNPK. Int J Biol Sci. 18:2032–2046. 2022. View Article : Google Scholar : PubMed/NCBI
5	Jiang W, Xia J, Xie S, Zou R, Pan S, Wang ZW, Assaraf YG and Zhu X: Long non-coding RNAs as a determinant of cancer drug resistance: Towards the overcoming of chemoresistance via modulation of lncRNAs. Drug Resist Updat. 50:1006832020. View Article : Google Scholar : PubMed/NCBI
6	Chu Z, Huo N, Zhu X, Liu H, Cong R, Ma L, Kang X, Xue C, Li J, Li Q, et al: FOXO3A-induced LINC00926 suppresses breast tumor growth and metastasis through inhibition of PGK1-mediated Warburg effect. Mol Ther. 29:2737–2753. 2021. View Article : Google Scholar : PubMed/NCBI
7	Huang Y, Mo W, Ding X and Ding Y: Long non-coding RNAs in breast cancer stem cells. Med Oncol. 40:1772023. View Article : Google Scholar : PubMed/NCBI
8	Karthikeyan SK, Xu N, Ferguson Rd JE, Rais-Bahrami S, Qin ZS, Manne U, Netto GJ, S Chandrashekar D and Varambally S: Identification of androgen response-related lncRNAs in prostate cancer. Prostate. 83:590–601. 2023. View Article : Google Scholar : PubMed/NCBI
9	Chen X, Luo R, Zhang Y, Ye S, Zeng X, Liu J, Huang D, Liu Y, Liu Q, Luo ML, et al: Long noncoding RNA DIO3OS induces glycolytic-dominant metabolic reprogramming to promote aromatase inhibitor resistance in breast cancer. Nat Commun. 13:71602022. View Article : Google Scholar : PubMed/NCBI
10	Zhou L, Jiang J, Huang Z, Jin P, Peng L, Luo M, Zhang Z, Chen Y, Xie N, Gao W, et al: Hypoxia-induced lncRNA STEAP3-AS1 activates Wnt/β-catenin signaling to promote colorectal cancer progression by preventing m⁶A-mediated degradation of STEAP3 mRNA. Mol Cancer. 21:1682022. View Article : Google Scholar : PubMed/NCBI
11	Tong X, Gu PC, Xu SZ and Lin XJ: Long non-coding RNA-DANCR in human circulating monocytes: A potential biomarker associated with postmenopausal osteoporosis. Biosci Biotechnol Biochem. 79:732–737. 2015. View Article : Google Scholar : PubMed/NCBI
12	Gan X, Ding D, Wang M, Yang Y, Sun D, Li W, Ding W, Yang F, Zhou W and Yuan S: DANCR deletion retards the initiation and progression of hepatocellular carcinoma based on gene knockout and patient-derived xenograft in situ hepatoma mice model. Cancer Lett. 550:2159302022. View Article : Google Scholar : PubMed/NCBI
13	Lamere AT and Li J: Inference of gene co-expression networks from single-cell RNA-sequencing data. Methods Mol Biol. 1935:141–153. 2019. View Article : Google Scholar : PubMed/NCBI
14	Luo ZH, Walid AA, Xie Y, Long H, Xiao W, Xu L, Fu Y, Feng L and Xiao B: Construction and analysis of a dysregulated lncRNA-associated ceRNA network in a rat model of temporal lobe epilepsy. Seizure. 69:105–114. 2019. View Article : Google Scholar : PubMed/NCBI
15	Ruan Y, Li Y, Liu Y, Zhou J, Wang X and Zhang W: Investigation of optimal pathways for preeclampsia using network-based guilt by association algorithm. Exp Ther Med. 17:4139–4143. 2019.PubMed/NCBI
16	Thiel D, Conrad ND, Ntini E, Peschutter RX, Siebert H and Marsico A: Identifying lncRNA-mediated regulatory modules via ChIA-PET network analysis. BMC Bioinformatics. 20:2922019. View Article : Google Scholar : PubMed/NCBI
17	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
18	Zhong G, Su S, Li J, Zhao H, Hu D, Chen J, Li S, Lin Y, Wen L, Lin X, et al: Activation of Piezo1 promotes osteogenic differentiation of aortic valve interstitial cell through YAP-dependent glutaminolysis. Sci Adv. 9:eadg04782023. View Article : Google Scholar : PubMed/NCBI
19	Xiao YF, Li BS, Liu JJ, Wang SM, Liu J, Yang H, Hu YY, Gong CL, Li JL and Yang SM: Role of lncSLCO1C1 in gastric cancer progression and resistance to oxaliplatin therapy. Clin Transl Med. 12:e6912022. View Article : Google Scholar : PubMed/NCBI
20	Tao W, Wang C, Zhu B, Zhang G and Pang D: LncRNA DANCR contributes to tumor progression via targetting miR-216a-5p in breast cancer: lncRNA DANCR contributes to tumor progression. Biosci Rep. 39:BSR201816182019. View Article : Google Scholar : PubMed/NCBI
21	Bi Y, Guo S, Xu X, Kong P, Cui H, Yan T, Ma Y, Cheng Y, Chen Y, Liu X, et al: Decreased ZNF750 promotes angiogenesis in a paracrine manner via activating DANCR/miR-4707-3p/FOXC2 axis in esophageal squamous cell carcinoma. Cell Death Dis. 11:2962020. View Article : Google Scholar : PubMed/NCBI
22	Pan Z, Wu C, Li Y, Li H, An Y, Wang G, Dai J and Wang Q: LncRNA DANCR silence inhibits SOX5-medicated progression and autophagy in osteosarcoma via regulating miR-216a-5p. Biomed Pharmacother. 122:1097072020. View Article : Google Scholar : PubMed/NCBI
23	Hu X, Peng WX, Zhou H, Jiang J, Zhou X, Huang D, Mo YY and Yang L: IGF2BP2 regulates DANCR by serving as an N6-methyladenosine reader. Cell Death Differ. 27:1782–1794. 2020. View Article : Google Scholar : PubMed/NCBI
24	Xiong M, Wu M, Peng D, Huang W, Chen Z, Ke H, Chen Z, Song W, Zhao Y, Xiang AP, et al: LncRNA DANCR represses Doxorubicin-induced apoptosis through stabilizing MALAT1 expression in colorectal cancer cells. Cell Death Dis. 12:242021. View Article : Google Scholar : PubMed/NCBI
25	Zhang X, Xie K, Zhou H, Wu Y, Li C, Liu Y, Liu Z, Xu Q, Liu S, Xiao D and Tao Y: Role of non-coding RNAs and RNA modifiers in cancer therapy resistance. Mol Cancer. 19:472020. View Article : Google Scholar : PubMed/NCBI
26	Yang ZJ, Liu R, Han XJ, Qiu CL, Dong GL, Liu ZQ, Liu LH, Luo Y and Jiang LP: Knockdown of the long non-coding RNA MALAT1 ameliorates TNF-α-mediated endothelial cell pyroptosis via the miR-30c-5p/Cx43 axis. Mol Med Rep. 27:902023. View Article : Google Scholar : PubMed/NCBI
27	Shi SJ, Wang LJ, Yu B, Li YH, Jin Y and Bai XZ: LncRNA-ATB promotes trastuzumab resistance and invasion-metastasis cascade in breast cancer. Oncotarget. 6:11652–11663. 2015. View Article : Google Scholar : PubMed/NCBI
28	Xue X, Yang YA, Zhang A, Fong KW, Kim J, Song B, Li S, Zhao JC and Yu J: LncRNA HOTAIR enhances ER signaling and confers tamoxifen resistance in breast cancer. Oncogene. 35:2746–2755. 2016. View Article : Google Scholar : PubMed/NCBI
29	Ghafouri-Fard S, Khoshbakht T, Hussen BM, Baniahmad A, Taheri M and Samadian M: A review on the role of DANCR in the carcinogenesis. Cancer Cell Int. 22:1942022. View Article : Google Scholar : PubMed/NCBI
30	Xu Y, Bao Y, Qiu G, Ye H, He M and Wei X: METTL3 promotes proliferation and migration of colorectal cancer cells by increasing SNHG1 stability. Mol Med Rep. 28:2172023. View Article : Google Scholar : PubMed/NCBI
31	Xue ST, Zheng B, Cao SQ, Ding JC, Hu GS, Liu W and Chen C: Long non-coding RNA LINC00680 functions as a ceRNA to promote esophageal squamous cell carcinoma progression through the miR-423-5p/PAK6 axis. Mol Cancer. 21:692022. View Article : Google Scholar : PubMed/NCBI
32	Ghaemi Z, Mowla SJ and Soltani BM: Novel splice variants of LINC00963 suppress colorectal cancer cell proliferation via miR-10a/miR-143/miR-217/miR-512-mediated regulation of PI3K/AKT and Wnt/β-catenin signaling pathways. Biochim Biophys Acta Gene Regul Mech. 1866:1949212023. View Article : Google Scholar : PubMed/NCBI
33	Yang S, Wang X, Zhou X, Hou L, Wu J, Zhang W, Li H, Gao C and Sun C: ncRNA-mediated ceRNA regulatory network: Transcriptomic insights into breast cancer progression and treatment strategies. Biomed Pharmacother. 162:1146982023. View Article : Google Scholar : PubMed/NCBI
34	Zhou Y, Meng X, Chen S, Li W, Li D, Singer R and Gu W: IMP1 regulates UCA1-mediated cell invasion through facilitating UCA1 decay and decreasing the sponge effect of UCA1 for miR-122-5p. Breast Cancer Res. 20:322018. View Article : Google Scholar : PubMed/NCBI
35	Jiang N, Wang X, Xie X, Liao Y, Liu N, Liu J, Miao N, Shen J and Peng T: lncRNA DANCR promotes tumor progression and cancer stemness features in osteosarcoma by upregulating AXL via miR-33a-5p inhibition. Cancer Lett. 405:46–55. 2017. View Article : Google Scholar : PubMed/NCBI
36	Lu G, Li Y, Ma Y, Lu J, Chen Y, Jiang Q, Qin Q, Zhao L, Huang Q, Luo Z, et al: Long noncoding RNA LINC00511 contributes to breast cancer tumourigenesis and stemness by inducing the miR-185-3p/E2F1/Nanog axis. J Exp Clin Cancer Res. 37:2892018. View Article : Google Scholar : PubMed/NCBI
37	Tao WY, Wang CY, Sun YH, Su YH, Pang D and Zhang GQ: MicroRNA-34c suppresses breast cancer migration and invasion by targeting GIT1. J Cancer. 7:1653–1662. 2016. View Article : Google Scholar : PubMed/NCBI
38	Zhang S, Miyakawa A, Wickström M, Dyberg C, Louhivuori L, Varas-Godoy M, Kemppainen K, Kanatani S, Kaczynska D, Ellström ID, et al: GIT1 protects against breast cancer growth through negative regulation of Notch. Nat Commun. 13:15372022. View Article : Google Scholar : PubMed/NCBI
39	Zhang J, Zhang J, Liu W, Ge R, Gao T, Tian Q, Mu X, Zhao L and Li X: UBTF facilitates melanoma progression via modulating MEK1/2-ERK1/2 signalling pathways by promoting GIT1 transcription. Cancer Cell Int. 21:5432021. View Article : Google Scholar : PubMed/NCBI