Abstract：Objective: To investigate the effect of HOXC10 on the stem cell-like characteristics of lung cancer cells through targeted regulation of CST1 expression. Methods: TLung cancer cell line A549 was cultured under serum-free conditions to form tumour spheres.WB detected the expression of HOXC10 and stemness marker proteins CD44,CD133,Nanog,SOX2 and OCT4 respectively.ShNC and ShHOXC10 A549 cells were constructed to detect the expression of stemness marker proteins CD44,CD133,Nanog,SOX2 and OCT4,tumour sphere-forming assay to detect cell self-renewal ability and CCK8 assay to detect cell proliferation ability.ShNC and ShHOXC10 lung cancer mouse subcutaneous tumour models were constructed,tumour volume and weight were measured,and the expression of HOXC10,CST1 and stemness marker proteins CD44 and CD133 were detected in tumour tissues by immunohistochemistry.CST1 mRNA and protein expression in A549 cells of ShNC and ShHOXC10 groups were detected by qPCR and WB.ChIP-PCR and ChIP-qPCR were used to detect HOXC10 and CST1 promoter sequence binding,and dual luciferase reporter genes were used to verify the regulation of CST1 promoter activity by HOXC10.The effect of CST1 overexpression on the expression of stemness marker proteins CD44,CD133,Nanog,SOX2,OCT4 and tumour spheroid formation and cell proliferation was examined by back-complementing pcDNA3.1-CST1 in ShHOXC10 cells. Results: HOXC10 was highly expressed in the tumour spheres of A549 cells,and knockdown of HOXC10 significantly inhibited the expression of stemness protein markers CD44,CD133,Nanog,SOX2,and OCT4,inhibiting the proliferation and tumour sphere-forming ability of A549 cells.Subcutaneous tumour assays showed that knockdown of HOXC10 inhibited the tumour-forming ability of A549 cells (P<0.001) and tumour weight (P<0.0001) and volume (P<0.01) were significantly reduced. Conclusion: HOXC10 regulates the stem cell-like properties of lung cancer cells through CST1.
康建军, 高乐, 席俊峰. HOXC10通过靶向调控CST1的表达对肺癌细胞干细胞样特性的作用研究[J]. 河北医学, 2022, 28(7): 1071-1076.
KANG Jianjun, GAO Le, XI Junfeng. Study of the Effect of HOXC10 on the Stem Cell-Like Properties of Lung Cancer Cells Through Targeted Regulation of CST1 Expression. HeBei Med, 2022, 28(7): 1071-1076.
[1] Clinton S K,Giovannucci E L,Hursting S D.The world cancer research fund/American institute for cancer research third expert report on diet,nutrition,physical activity,and cancer:impact and future directions [J].Nutr,2020,150(4):663-671. [2] Hosseinirad H,Rashidi M,Moghaddam M M,et al.Stem cell therapy for lung diseases:From fundamental aspects to clinical applications [J].Cell Mol Biol (Noisy-le-grand),2018,64(10):92-101. [3] Li M,Alsager J S,Wang Z,et al.Epigenetic upregulation of HOXC10 in non-small lung cancer cells [J].Aging (Albany NY),2020,12(17):16921-16935. [4] Dai D N,Li Y,Chen B,et al.Elevated expression of CST1 promotes breast cancer progression and predicts a poor prognosis [J].Mol Med (Berl),2017,95(8):873-886. [5] Ding J,Wang X,Gao J,et al.Silencing of cystatin SN abrogates cancer progression and stem cell properties in papillary thyroid carcinoma [J].FEBS Open Bio,2021,11(8):2186-2197. [6] Kim J,Bae D H,Kim J H,et al.HOXC10 overexpression promotes cell proliferation and migration in gastric cancer [J].Oncol Rep,2019,42(1):202-212. [7] Ma M,Wang C,Ao Y,et al.HOXC10 promotes proliferation and attenuates lipid accumulation of sheep bone marrow mesenchymal stem cells [J].Mol Cell Probes,2020,49:101491. [8] Li G,Han N,Yang H,et al.Homeobox C10 inhibits the osteogenic differentiation potential of mesenchymal stem cells [J].Connect Tissue Res,2018,59(3):201-211.
2022, Vol. 28 
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