Article Data

  • Views 2306
  • Dowloads 158

Original Research

Open Access

Meis1 restrains the growth and epithelial-mesenchymal transition of breast cancer cells through the HOXB13/PI3K/AKT signaling pathway

  • Wanqiong Zheng1,*,
  • Ye Tian2
  • Yiming Zhang1
  • Binnan Li1

1General Surgery, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, 325000 Wenzhou, Zhejiang, China

2Department of Oncology, Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine, 712000 Xianyang, Shaanxi, China

DOI: 10.22514/ejgo.2024.124 Vol.45,Issue 6,December 2024 pp.117-123

Submitted: 20 May 2024 Accepted: 17 July 2024

Published: 15 December 2024

*Corresponding Author(s): Wanqiong Zheng E-mail: zwq5171717@163.com

Abstract

Breast cancer (BC) is one hackneyed malignant tumor occurred on breast in female and possesses a higher mortality. Meis1 serves as a homeobox (HOX)-family transcription factor, and has been disclosed to take part into the modulation of diseases’ progression. However, the detailed impacts and associated regulatory pathway of Meis1 in BC progression keep dimness. The protein expressions were inspected through western blot. The cell viability and proliferation were determined through cell counting kit-8 (CCK-8) and colony formation assays. The cell apoptosis was determined through flow cytometry. The cellular morphological changes were verified through Phalloidin staining. The interaction between Meis1 and HOXB13 was confirmed through co-immunoprecipitation (Co-IP) assay. In this study, Meis1 expression was down-regulated in BRCA (breast invasive carcinoma) tissues from gene expression profiling interactive analysis (GEPIA) online database. And, it was uncovered that Meis1 existed the lower expression in BC cell lines. Besides, amplification of Meis1 restrained cell growth and aggrandized cell apoptosis in BC. Additionally, augmentation of Meis1 weakened epithelial-mesenchymal transition (EMT) process in BC through augmenting E-cadherin as well as declining neural cadherin (N-cadherin) and α-smooth muscle actin (α-SMA) expressions. Lastly, it was uncovered that overexpression of Meis1 retarded the HOXB13/phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway. To sum up, this study revealed that Meis1 restrained cell proliferation and epithelial-mesenchymal transition (EMT) process in BC through the HOXB13/PI3K/AKT signaling pathway. This work suggested that Meis1 may be one available molecular target for the amelioration of BC.


Keywords

Meis1; Breast cancer; Epithelial-mesenchymal transition; HOXB13/PI3K/AKT pathway


Cite and Share

Wanqiong Zheng,Ye Tian,Yiming Zhang,Binnan Li. Meis1 restrains the growth and epithelial-mesenchymal transition of breast cancer cells through the HOXB13/PI3K/AKT signaling pathway. European Journal of Gynaecological Oncology. 2024. 45(6);117-123.

References

[1] Barzaman K, Karami J, Zarei Z, Hosseinzadeh A, Kazemi MH, Moradi-Kalbolandi S, et al. Breast cancer: biology, biomarkers, and treatments. International Immunopharmacology. 2020; 84: 106535.

[2] Rodgers RJ, Reid GD, Koch J, Deans R, Ledger WL, Friedlander M, et al. The safety and efficacy of controlled ovarian hyperstimulation for fertility preservation in women with early breast cancer: a systematic review. Human Reproduction. 2017; 32: 1033–1045.

[3] Fan L, Strasser-Weippl K, Li JJ, St Louis J, Finkelstein DM, Yu KD, et al. Breast cancer in China. The Lancet. 2014; 15: e279–e289.

[4] Lefrère H, Moore K, Floris G, Sanders J, Seignette IM, Bismeijer T, et al. Poor outcome in postpartum breast cancer patients is associated with distinct molecular and immunologic features. Clinical Cancer Research. 2023; 29: 3729–3743.

[5] Yao M, Gu Y, Yang Z, Zhong K, Chen Z. MEIS1 and its potential as a cancer therapeutic target (Review). International Journal of Molecular Medicine. 2021; 48: 181.

[6] Rani A, Greenlaw R, Smith RA, Galustian C. HES1 in immunity and cancer. Cytokine & Growth Factor Reviews. 2016; 30: 113–117.

[7] Zhou D, Yang Q, Li J, Liu X, Li J, Zhou W, et al. Loss of Hes1 in embryonic stem cells caused developmental disorders in retinal pigment epithelium morphogenesis and specification. Biochemical and Biophysical Research Communications. 2022; 632: 76–84.

[8] Kocabas F, Zheng J, Thet S, Copeland NG, Jenkins NA, DeBerardinis RJ, et al. Meis1 regulates the metabolic phenotype and oxidant defense of hematopoietic stem cells. Blood. 2012; 120: 4963–4972.

[9] Li W, Huang K, Guo H, Cui G. Meis1 regulates proliferation of non-small-cell lung cancer cells. Journal of Thoracic Disease. 2014; 6: 850–855.

[10] Zhu J, Cui L, Xu A, Yin X, Li F, Gao J. MEIS1 inhibits clear cell renal cell carcinoma cells proliferation and in vitro invasion or migration. BMC Cancer. 2017; 17: 176.

[11] Li Y, Gan Y, Liu J, Li J, Zhou Z, Tian R, et al. Downregulation of MEIS1 mediated by ELFN1-AS1/EZH2/DNMT3a axis promotes tumorigenesis and oxaliplatin resistance in colorectal cancer. Signal Transduction and Targeted Therapy. 2022; 7: 87.

[12] Garcia-Cuellar MP, Prinz A, Slany RK. Meis1 supports leukemogenesis through stimulation of ribosomal biogenesis and Myc. Haematologica. 2022; 107: 2601–2616.

[13] Doolan P, Clynes M, Kennedy S, Mehta JP, Germano S, Ehrhardt C, et al. TMEM25, REPS2 and Meis 1: favourable prognostic and predictive biomarkers for breast cancer. Tumour Biology. 2009; 30: 200–209.

[14] Dard A, Reboulet J, Jia Y, Bleicher F, Duffraisse M, Vanaker JM, et al. Human hox proteins use diverse and context-dependent motifs to interact with tale class cofactors. Cell Reports. 2018; 22: 3058–3071.

[15] Dongre A, Weinberg RA. New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer. Nature Reviews Molecular Cell Biology. 2019; 20: 69–84.

[16] Tanabe S. Epithelial-mesenchymal transition and cancer stem cells. Advances in Experimental Medicine and Biology. 2022; 1393: 1–49.

[17] Xu Z, Zhang Y, Dai H, Han B. Epithelial-mesenchymal transition-mediated tumor therapeutic resistance. Molecules. 2022; 27: 4750.

[18] Howley BV, Mohanty B, Dalton A, Grelet S, Karam J, Dincman T, et al. The ubiquitin E3 ligase ARIH1 regulates hnRNP E1 protein stability, EMT and breast cancer progression. Oncogene. 2022; 41: 1679–1690.

[19] Yang SY, Xie YF, Zhang TM, Deng L, Liao L, Hu SY, et al. Inositol monophosphatase 1 (IMPA1) promotes triple-negative breast cancer progression through regulating mTOR pathway and EMT process. Cancer Medicine. 2023; 12: 1602–1615.

[20] Zheng B, Du P, Zeng Z, Cao P, Ma X, Jiang Y. Propranolol inhibits EMT and metastasis in breast cancer through miR-499-5p-mediated Sox6. Journal of Cancer Research and Clinical Oncology. 2024; 150: 59.

[21] Li B, Huang L, Ruan J. PKMYT1 promotes epithelial-mesenchymal transition process in triple-negative breast cancer by activating notch signaling. Revista de Investigación Clínica. 2024; 76: 45–59.

[22] Johng D, Torga G, Ewing CM, Jin K, Norris JD, McDonnell DP, et al. HOXB13 interaction with MEIS1 modifies proliferation and gene expression in prostate cancer. The Prostate. 2019; 79: 414–424.

[23] Whitlock NC, Trostel SY, Wilkinson S, Terrigino NT, Hennigan ST, Lake R, et al. MEIS1 down-regulation by MYC mediates prostate cancer development through elevated HOXB13 expression and AR activity. Oncogene. 2020; 39: 5663–5674.

[24] Y Yan W, Ma X, Zhao X, Zhang S. Baicalein induces apoptosis and autophagy of breast cancer cells via inhibiting PI3K/AKT pathway in vivo and vitro. Drug Design, Development and Therapy. 2018; 12: 3961–3972.

[25] Huang S, Huang P, Wu H, Wang S, Liu G. LINC02381 aggravates breast cancer through the miR-1271-5p/FN1 axis to activate PI3K/AKT pathway. Molecular Carcinogenesis. 2022; 61: 346–358.

[26] Qiao L, Dong C, Ma B. UBE2T promotes proliferation, invasion and glycolysis of breast cancer cells by regualting the PI3K/AKT signaling pathway. Journal of Receptors and Signal Transduction. 2022; 42: 151–159.

[27] Xiang K, Yanshan H, Chunmei Z, Minmin G, Yan W, Xiaojia Y. GP5 regulates epithelial-mesenchymal transition in breast cancer via the PI3K/AKT signaling pathway. Experimental Biology and Medicine. 2022; 247: 1501–1517.

[28] Guo C, Chu H, Gong Z, Zhang B, Li C, Chen J, et al. HOXB13 promotes gastric cancer cell migration and invasion via IGF-1R upregulation and subsequent activation of PI3K/AKT/mTOR signaling pathway. Life Sciences. 2021; 278: 119522.


Submission Turnaround Time

Top