Transcription factor KLF16 activates MAGT1 to regulate the tumorigenesis and progression of breast cancer

Li,Lin; Zhang,Xi; Li,Yuqi; Xiao,Bo; Pei,Sibiao; Jiang,Hangyu; Zhang,Xiaofen

doi:10.3892/ijmm.2022.5171

Transcription factor KLF16 activates MAGT1 to regulate the tumorigenesis and progression of breast cancer

Authors:
- Lin Li
- Xi Zhang
- Yuqi Li
- Bo Xiao
- Sibiao Pei
- Hangyu Jiang
- Xiaofen Zhang
View Affiliations

Affiliations: Key Laboratory for Biorheological Science and Technology of Ministry of Education, Bioengineering College of Chongqing University, Chongqing 400044, P.R. China, Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, P.R. China, Department of Pharmacy, The Second Clinical Medical College of North Sichuan Medical College, Nanchong, Sichuan 637003, P.R. China, Department of Oncology, Nanchong Jialing District People's Hospital, Nanchong, Sichuan 637931, P.R. China, Department of Oncology, The Second Clinical Medical College of North Sichuan Medical College, Nanchong, Sichuan 637003, P.R. China
Published online on: July 7, 2022 https://doi.org/10.3892/ijmm.2022.5171
Article Number: 115
Copyright: © Li 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

Breast cancer is the most frequent cause of cancer‑related mortality among women worldwide. The present study aimed to explore the role of magnesium transporter protein 1 (MAGT1) in breast cancer and to illustrate the potential underlying molecular mechanisms. Bioinformatic analysis was performed to explore the association between MAGT1 expression and patients with breast cancer. MTT, colony formation, wound healing and Transwell assays were performed to examine the proliferative, migratory and invasive abilities of MCF‑7 cells. Western blot analysis was conducted to determine the corresponding protein expression. Chromatin immunoprecipitation and luciferase reporter assays were carried out to reveal the interaction between MAGT1 and the Kruppel‑like factor 16 (KLF16). In addition, an experimental animal model was established by the subcutaneous injection of MCF‑7 cells into BALB/c nude mice, and tumor weight and size were measured. The results revealed that MAGT1 expression was upregulated in breast cancer. MAGT1 knockdown significantly suppressed the MCF‑7 cell proliferative, migratory and invasive abilities, and downregulated the protein expression of Ki67, proliferating cell nuclear antigen, MMP2 and MMP9. MAGT1 knockdown also markedly suppressed tumor growth in vivo. Moreover, KLF6 could bind to the MAGT1 promoter and positively regulate MAGT1 expression. The inhibitory effects of KLF6 knockdown on cell proliferation, migration and invasion in vitro, and tumor growth in vivo were partly abolished by MAGT1 overexpression. On the whole, the findings of the present study suggest that MAGT1 knockdown exerts notable inhibitory effects on the progression of breast cancer, providing a potential therapeutic target for the treatment of breast cancer.

View Figures

View References

1	Khan F, Rahman A and Carrier M: Occult cancer detection in venous thromboembolism: The past, the present, and the future. Res Pract Thromb Haemost. 1:9–13. 2017. View Article : Google Scholar
2	Davari M, Amani B, Mokarian F, Hoseini M, Akbarzadeh A and Heidarzadeh Khoramabadi N: Effectiveness of trastuzumab as adjuvant therapy in patients with early stage breast cancer: A systematic review and meta-analysis. Med J Islam Repub Iran. 31:882017. View Article : Google Scholar
3	Peart O: Metastatic breast cancer. Radiol Technol. 88:519M–539M. 2017.PubMed/NCBI
4	Tian T, Wang M, Lin S, Guo Y, Dai Z, Liu K, Yang P, Dai C, Zhu Y, Zheng Y, et al: The impact of lncRNA dysregulation on clinicopathology and survival of breast cancer: A systematic review and meta-analysis. Mol Ther Nucleic Acids. 12:359–369. 2018. View Article : Google Scholar : PubMed/NCBI
5	Shamsi M and Pirayesh Islamian J: Breast cancer: Early diagnosis and effective treatment by drug delivery tracing. Nucl Med Rev Cent East Eur. 20:45–48. 2017. View Article : Google Scholar : PubMed/NCBI
6	Hammerl D, Smid M, Timmermans AM, Sleijfer S, Martens JWM and Debets R: Breast cancer genomics and immuno-oncological markers to guide immune therapies. Semin Cancer Biol. 52:178–188. 2018. View Article : Google Scholar
7	Walker-Smith TL and Peck J: Genetic and genomic advances in breast cancer diagnosis and treatment. Nurs Womens Health. 23:518–525. 2019. View Article : Google Scholar : PubMed/NCBI
8	Zheng JM, Kong YY, Li YY and Zhang W: MagT1 regulated the odontogenic differentiation of BMMSCs induced byTGC-CM via ERK signaling pathway. Stem Cell Res Ther. 10:482019. View Article : Google Scholar : PubMed/NCBI
9	Goytain A and Quamme GA: Identification and characterization of a novel mammalian Mg²⁺ transporter with channel-like properties. BMC Genomics. 6:482005. View Article : Google Scholar
10	Chaigne-Delalande B, Li FY, O'Connor GM, Lukacs MJ, Jiang P, Zheng L, Shatzer A, Biancalana M, Pittaluga S, Matthews HF, et al: Mg²⁺ regulates cytotoxic functions of NK and CD8 T cells in chronic EBV infection through NKG2D. Science. 341:186–191. 2013. View Article : Google Scholar : PubMed/NCBI
11	Wang G, Li Y, Li J, Zhang D, Luo C, Zhang B and Sun X: microRNA-199a-5p suppresses glioma progression by inhibiting MAGT1. J Cell Biochem. 120:15248–15254. 2019. View Article : Google Scholar : PubMed/NCBI
12	Zheng K, Yang Q, Xie L, Qiu Z, Huang Y, Lin Y, Tu L and Cui C: Overexpression of MAGT1 is associated with aggressiveness and poor prognosis of colorectal cancer. Oncol Lett. 18:3857–3862. 2019.PubMed/NCBI
13	Philipsen S and Suske G: A tale of three fingers: The family of mammalian Sp/XKLF transcription factors. Nucleic Acids Res. 27:2991–3000. 1999. View Article : Google Scholar : PubMed/NCBI
14	Kaczynski J, Cook T and Urrutia R: Sp1- and Kruppel-like transcription factors. Genome Biol. 4:2062003. View Article : Google Scholar
15	Sun N, Shen C, Zhang L, Wu X, Yu Y, Yang X, Yang C, Zhong C, Gao Z, Miao W, et al: Hepatic Krüppel-like factor 16 (KLF16) targets PPARα to improve steatohepatitis and insulin resistance. Gut. 70:2183–2195. 2021. View Article : Google Scholar
16	Yang X, Chen Q, Sun L, Zhang H, Yao L, Cui X, Gao Y, Fang F and Chang Y: KLF10 transcription factor regulates hepatic glucose metabolism in mice. Diabetologia. 60:2443–2452. 2017. View Article : Google Scholar : PubMed/NCBI
17	Cui A, Fan H, Zhang Y, Zhang Y, Niu D, Liu S, Liu Q, Ma W, Shen Z, Shen L, et al: Dexamethasone-induced Krüppel-like factor 9 expression promotes hepatic gluconeogenesis and hyperglycemia. J Clin Invest. 129:2266–2278. 2019. View Article : Google Scholar : PubMed/NCBI
18	Ma P, Sun CQ, Wang YF, Pan YT, Chen QN, Liu WT, Liu J, Zhao CH, Shu YQ and Li W: KLF16 promotes proliferation in gastric cancer cells via regulating p21 and CDK4. Am J Transl Res. 9:3027–3036. 2017.PubMed/NCBI
19	Bang S, Li J, Zhang M, Cui R, Wu X, Xin Z, Ma D, Zhang J and Zhang H: The clinical relevance and function of Krüppel-like factor 16 in breast cancer. Cancer Manag Res. 12:6373–6383. 2020. View Article : Google Scholar :
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
21	Harbeck N and Gnant M: Breast cancer. Lancet. 389:1134–1150. 2017. View Article : Google Scholar
22	Kozlowski J, Kozłowska A and Kocki J: Breast cancer metastasis-insight into selected molecular mechanisms of the phenomenon. Postepy Hig Med Dosw (Online). 69:447–451. 2015. View Article : Google Scholar
23	Osborne C, Wilson P and Tripathy D: Oncogenes and tumor suppressor genes in breast cancer: Potential diagnostic and therapeutic applications. Oncologist. 9:361–377. 2004. View Article : Google Scholar : PubMed/NCBI
24	Sung NJ, Kim NH, Surh YJ and Park SA: Gremlin-1 promotes metastasis of breast cancer cells by activating STAT3-MMP13 signaling pathway. Int J Mol Sci. 21:92272020. View Article : Google Scholar :
25	Li J, Guo Y, Duan L, Hu X, Zhang X, Hu J, Huang L, He R, Hu Z, Luo W, et al: AKR1B10 promotes breast cancer cell migration and invasion via activation of ERK signaling. Oncotarget. 8:33694–33703. 2017. View Article : Google Scholar : PubMed/NCBI
26	de Baaij JH, Hoenderop JG and Bindels RJ: Magnesium in man: Implications for health and disease. Physiol Rev. 95:1–46. 2015. View Article : Google Scholar
27	Li H, Xia T, Guan Y and Yu Y: Sevoflurane regulates glioma progression by Circ_0002755/miR-628-5p/MAGT1 axis. Cancer Manag Res. 12:5085–5098. 2020. View Article : Google Scholar : PubMed/NCBI
28	Bi C, Zhang X, Chen Y, Dong Y, Shi Y, Lei Y, Lv D, Cao X, Li W and Shi H: MAGT1 is required for HeLa cell proliferation through regulating p21 expression, S-phase progress and ERK/p38 MAPK MYC axis. Cell Cycle. 20:2233–2247. 2021. View Article : Google Scholar : PubMed/NCBI
29	Di Giammartino DC: Kloetgen A, Polyzos A, Liu Y, Kim D, Murphy D, Abuhashem A, Cavaliere P, Aronson B, Shah V, et al KLF4 is involved in the organization and regulation of pluripotency-associated three-dimensional enhancer networks. Nat Cell Biol. 21:1179–1190. 2019. View Article : Google Scholar : PubMed/NCBI
30	Lambert M, Jambon S, Depauw S and David-Cordonnier MH: Targeting transcription factors for cancer treatment. Molecules. 23:14792018. View Article : Google Scholar :
31	Yadav RK, Chauhan AS, Zhuang L and Gan B: FoxO transcription factors in cancer metabolism. Semin Cancer Biol. 50:65–76. 2018. View Article : Google Scholar : PubMed/NCBI
32	Yeung SJ, Pan J and Lee MH: Roles of p53, MYC and HIF-1 in regulating glycolysis-the seventh hallmark of cancer. Cell Mol Life Sci. 65:3981–3999. 2008. View Article : Google Scholar : PubMed/NCBI
33	Viatour P, Merville MP, Bours V and Chariot A: Phosphorylation of NF-kappaB and IkappaB proteins: Implications in cancer and inflammation. Trends Biochem Sci. 30:43–52. 2005. View Article : Google Scholar : PubMed/NCBI
34	Shields JM and Yang VW: Identification of the DNA sequence that interacts with the gut-enriched Krüppel-like factor. Nucleic Acids Res. 26:796–802. 1998. View Article : Google Scholar : PubMed/NCBI
35	Miller IJ and Bieker JJ: A novel, erythroid cell-specific murine transcription factor that binds to the CACCC element and is related to the Krüppel family of nuclear proteins. Mol Cell Biol. 13:2776–2786. 1993.PubMed/NCBI
36	Chen X, Li S, Ke Y, Wu S, Huang T, Hu W, Fu H and Guo X: KLF16 suppresses human glioma cell proliferation and tumourigenicity by targeting TFAM. Artif Cells Nanomed Biotechnol. 46(Suppl 1): S608–S615. 2018. View Article : Google Scholar