|
|
Effect of miR-145 on the proliferation, invasion and migration of triple-negative breast cancer cells#br# |
ZHU Lingxiao ZHANG Lan ZHANG Xuepeng LI Haoxin |
Department of Surgical Oncology, North China University of Science and Technology Affiliated Hospital, Hebei Province, Tangshan 063000, China |
|
|
Abstract Objective To investigate the effect of microRNA-145 (miR-145) on the proliferation, invasion, and migration of triple-negative breast cancer (TNBC) MDA-MB-231 cells. Methods MDA-MB-231 cells were divided into three groups, blank group (cells without special treatment), miR-145 NC group (transfected with miR-145 nonsense sequence), and miR-145 inhibitors group (transfected with miR-145 inhibitors). The relative expression levels of miR-145, adisintegrin and metalloproteinase 17 (ADAM17), and epidermal growth factor receptor (EGFR) mRNA were detected by real-time polymerase chain reaction, CCK-8 method was used to compare the proliferation ability of each group, Transwell test and scratch test were used to determine the invasion and migration ability of each group, and Western blot was used to detect the expression of ADAM17 and EGFR protein in each group. Results The expression level of miR-145 in miR-145 inhibitors group was lower than that in miR-145 NC group, and the difference was statistically significant (P < 0.05); there was no significant difference in miR-145 expression between miR-145 NC group and blank group (P > 0.05). At 24, 48 h, and 72 h after transfection, there were no significant differences in optical density (OD) values between miR-145 NC group and blank group (P > 0.05). At 72 h after transfection, OD value of miR-145 inhibitors group was higher than that of miR-145 NC group, and the difference was statistically significant (P < 0.05). At 24 and 48 h after transfection, there were no significant differences in OD values between miR-145 inhibitors group and miR-145 NC group (P > 0.05). The number of transmembrane cells in miR-145 inhibitors group was higher than that in miR-145 NC group, and the difference was statistically significant (P < 0.05); there was no significant difference in the number of transmembrane cells between miR-145 NC group and blank group (P > 0.05). The scratch healing rate in miR-145 inhibitors group was higher than that in miR-145 NC group, and the difference was statistically significant (P < 0.05); there was no significant difference in cell healing rate between miR-145 NC group and blank group (P > 0.05). The relative expression of ADAM17 mRNA in miR-145 inhibitors group was higher than that in miR-145 NC group, and the difference was statistically significant (P < 0.05); there was no significant difference in the relative expression of ADAM17 mRNA between miR-145 NC group and blank group(P > 0.05). There was no significant difference in the relative expression of EGFR mRNA between the miR-145 inhibitors group and miR-145 NC group (P > 0.05); there was no significant difference in the relative expression of EGFR mRNA between miR-145 NC group and blank group (P > 0.05). The relative expression levels of ADAM17 and EGFR protein in miR-145 inhibitors group were higher than those in miR-145 NC group, and the differences were statistically significant (P < 0.05); the relative expression levels of ADAM17 and EGFR protein in miR-145 NC group and blank group were not significantly different (P > 0.05). Conclusion After transfection of MDA-MB-231 cells with miR-145 inhibitors, the targeted activation of ADAM17/EGFR pathway promoted the proliferation, invasion and migration of MDA-MB-231 cells.
|
|
|
|
|
[1] Ma D,Jiang YZ,Xiao Y,et al. Integrated molecular profiling of young and elderly patients with triple-negative breast cancer indicates different biological bases and clinical management strategies [J]. Cancer,2020,126(14):3209-3218.
[2] Zhang G. Expression and prognostic significance of BANF1 in triple-negative breast cancer [J]. Cancer Manag Res,2020,12(12):145-150.
[3] Piasecka D,Braun M,Kordek R,et al. MicroRNAs in regulation of triple-negative breast cancer progression [J]. J Cancer Res Clin Oncol,2018,144(8):1401-1411.
[4] Ding L,Gu H,Xiong X,et al. MicroRNAs involved in carcinogenesis,prognosis,therapeutic resistance and applications in human triple-negative breast cancer [J]. Cells,2019,8(12):1492.
[5] Shen H,Li L,Zhou S,et al. The role of ADAM17 in tumorigenesis and progression of breast cancer [J]. Tumor Biol,2016,37(12):15359-15370.
[6] 刘欢,李红昌,陈亚峰,等.微小RNA在三阴性乳腺癌中的研究进展[J].中国普外基础与临床杂志,2020,27(1):103-106.
[7] Takahashi S,Thike AA,Koh VCY,et al. Triple-negative and HER2 positive ductal carcinoma in situ of the breast:characteristics,behavior and biomarker profile [J]. Virchows Arch,2018,47(33):275-283.
[8] Schmid P,Cortes J,Pusztai L,et al. Pembrolizumab for early triple-negative breast cancer [J]. N Engl J Med,2020, 382(9):810-821.
[9] Williams M,Cheng Y,Blenkiron C,et al. Exploring mechanisms of microRNA downregulation in cancer [J]. Microrna,2017,6(1):2-16.
[10] Yi M,Xu L,Jiao Y,et al. The role of cancer-derived microRNAs in cancer immune escape [J]. J Hematol Oncol,2020,13(1):25.
[11] Boufraqech M,Zhang L,Jain M,et al. MiR-145 suppresses thyroid cancer growth and metastasis and targets AKT3 [J]. Endocr Relat Cancer,2014,21(4):517-531.
[12] Li Q,Tong D,Guo C,et al. MicroRNA-145 suppresses gastric cancer progression by targeting Hu-antigen R [J]. Am J Physiol Cell Physiol,2020,318(3):605-614.
[13] Sheng N,Tan G,You W,et al. MiR-145 inhibits human colorectal cancer cell migration and invasion via PAK4-dependent pathway [J]. Cancer Med,2017,6(6):1331-1340.
[14] Zeinali T,Mansoori B,Mohammadi A,et al. Regulatory mechanisms of miR-145 expression and the importance of its function in cancer metastasis [J]. Biomed Pharmacother,2019,109:195-207.
[15] Ye P,Shi Y,An N,et al. MiR-145 overexpression triggers alteration of the whole transcriptome and inhibits breast cancer development [J]. Biomed Pharmacother,2018, 100:72-82.
[16] 张兰,郑健,张雪鹏,等.MiR-145通过调控解聚素-金属蛋白酶17对MCF-7乳腺癌细胞的影响[J].医学研究生学报,2019,32(11):1169-1173.
[17] Wu J,Yin LI,Jiang N,et al. MiR-145,a microRNA targeting ADAM17,inhibits the invasion and migration of nasopharyngeal carcinoma cells [J]. Exp Cell Res,2015, 338(2):232-238.
[18] Guo Y,He X,Zhang M,et al. Reciprocal control of ADA M17/EGFR/Akt signaling and miR-145 drives GBM invasiveness [J]. J Neurooncol,2020,147(2):327-337.
[19] Jia N,Liu J,Zhu G,et al. Polarization of ADAM17-driven EGFR signaling in electric field-guided collective migration of epidermal sheets [J]. J Cell Mol Med,2020, 24(23):14073-14085.
[20] Ni P,Yu M,Zhang R,et al. Prognostic significance of ADAM17 for gastric cancer survival:a meta-analysis [J]. Medicina,2020,56(7):322.
[21] Soto-Gamez A,Chen D,Nabuurs AGE,et al. A bispecific inhibitor of the EGFR/ADAM17 axis decreases cell proliferation and migration of EGFR-dependent cancer cells [J]. Cancers,2020,12(2):411. |
|
|
|