Int J Biol Sci 2023; 19(1):89-103. doi:10.7150/ijbs.74227 This issue Cite

Research Paper

miR-1275 targets MDK/AKT signaling to inhibit breast cancer chemoresistance by lessening the properties of cancer stem cells

Xu Han1,2*, Minghui Li1*, Jin Xu3*, Jingyue Fu1, Xinyang Wang4, Jingyi Wang5, Tiansong Xia1, Shui Wang1,2✉, Ge Ma1,2✉

1. Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, 210029, Nanjing, China.
2. Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, 211166, Nanjing, China.
3. Department of Breast and Thyroid Surgery, Nanjing First Hospital, Nanjing Medical University, 210029 Nanjing, China.
4. Department of Thyroid and Breast, The Second Affiliated Hospital of Nantong University, 226000, Nantong, China.
5. Department of Breast Surgery, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, 29 Xinglong Lane, 213003, Changzhou, China.
*These authors contributed equally to this work.

Citation:
Han X, Li M, Xu J, Fu J, Wang X, Wang J, Xia T, Wang S, Ma G. miR-1275 targets MDK/AKT signaling to inhibit breast cancer chemoresistance by lessening the properties of cancer stem cells. Int J Biol Sci 2023; 19(1):89-103. doi:10.7150/ijbs.74227. https://www.ijbs.com/v19p0089.htm
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Abstract

Graphic abstract

Chemoresistance is a major obstacle in the neoadjuvant chemotherapy (NCT) of locally advanced breast cancer (LABC). Identification of miRNAs as prognostic biomarkers may help overcome chemoresistance of breast cancer (BC). This study aimed to evaluate the expression level of miR-1275 in plasma samples and its biological functions in the chemoresistance of BC. The expression levels of miR-1275 in plasma samples and cells were measured by RT-qPCR. CRISPR/Cas9-mediated gene editing was used to construct miR-1275 knock-out cells in MCF-7. We found that miR-1275 was significantly downregulated in plasma from patients resistant to chemotherapy and in chemoresistant BC cell lines, while patients with low levels of miR-1275 showed poor overall survival. miR-1275 knock-out promoted chemoresistance in BC cells by increasing the properties of cancer stem cells (CSCs). Mechanistically, we identified that MDK was determined to be direct downstream protein of miR-1275 which initiated PI3K/Akt signaling in breast cancer cells. We demonstrated that the high expression level of miR-1275 in plasma predicted better response to NCT. The reduction of miR-1275 promoted BC cells chemoresistance by increasing CSCs properties via targeting MDK/AKT axis. The potential of miR-1275 as a new prognostic biomarker and therapeutic target of BC patients was identified.

Keywords: liquid biopsy, chemoresistance, miR-1275, CRISPR/Cas9, cancer stem cell


Citation styles

APA
Han, X., Li, M., Xu, J., Fu, J., Wang, X., Wang, J., Xia, T., Wang, S., Ma, G. (2023). miR-1275 targets MDK/AKT signaling to inhibit breast cancer chemoresistance by lessening the properties of cancer stem cells. International Journal of Biological Sciences, 19(1), 89-103. https://doi.org/10.7150/ijbs.74227.

ACS
Han, X.; Li, M.; Xu, J.; Fu, J.; Wang, X.; Wang, J.; Xia, T.; Wang, S.; Ma, G. miR-1275 targets MDK/AKT signaling to inhibit breast cancer chemoresistance by lessening the properties of cancer stem cells. Int. J. Biol. Sci. 2023, 19 (1), 89-103. DOI: 10.7150/ijbs.74227.

NLM
Han X, Li M, Xu J, Fu J, Wang X, Wang J, Xia T, Wang S, Ma G. miR-1275 targets MDK/AKT signaling to inhibit breast cancer chemoresistance by lessening the properties of cancer stem cells. Int J Biol Sci 2023; 19(1):89-103. doi:10.7150/ijbs.74227. https://www.ijbs.com/v19p0089.htm

CSE
Han X, Li M, Xu J, Fu J, Wang X, Wang J, Xia T, Wang S, Ma G. 2023. miR-1275 targets MDK/AKT signaling to inhibit breast cancer chemoresistance by lessening the properties of cancer stem cells. Int J Biol Sci. 19(1):89-103.

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