ALDH1A1 and miR-140: Potential Therapeutic Targets and Strategies for Cervical Cancer
Zinati Nuertai1, Rou Qian1, Zhang Meng1, Ming Jie3, Liu Ying1,2,*
1. Department of Special Needs Comprehensive,Afliated Cancer Hospital of Xinjiang Medical University,Urumqi 830011 Xinjiang,China;
2. Department of Oncology,Bachu County People's Hospital,Bachu 843800,Xinjiang,China
Abstract：Objective This study aimed to explore the expression levels of ALDH1A1 and miR-140 in cervical cancer cell lines and study their interactions.Through in-depth understanding of the mechanism of action of ALDH1A1 and miR-140 in the occurrence and development of cervical cancer,it provides new potential targets and treatment strategies for the diagnosis and treatment of cervical cancer. Methods Cervical cancer dataset was obtained from the NCBI GEO database,and R（3.5.0）software package Limma was used to screen Differentially Expressed Genes（DEGs）on the chip data.The selected differentially expressed genes were analyzed by Gene Ontology Biological Process（GO BP）function and Kyoto Encyclopedia of Genes and Genomes（KEGG）pathway,to construct the competing endogenous RNA network（ceRNA）of differential mRNA,microRNA and lncRNA;the protein-protein interaction network（PPI）of differential mRNA was constructed to select Hub genes.The Kaplan-Meier survival curve was drawn to understand its risk of disease,and cell experiments and qRT-PCR were performed to detect the expression levels of differential mRNA and target miRNA in each group of cells,and double luciferase experiments were performed to verify the interaction between the two. Results By analyzing the cervical cancer dataset in NCBI GEO database,the Hub gene ALDH1A1 was screened out and its miRNA was found.From the Kaplan-Meier curve,it was concluded that ALDH1A1 was a risk factor for the occurrence and development of cervical cancer,and the prognosis of the high expression group was significantly worse than that of the low expression group.The results of cell experiments showed that in cervical cancer cell lines,the expression level of ALDH1A1 was higher,while the expression level of miR-140 was lower.Further experiments showed that miR-140 could significantly inhibit the expression of ALDH1A1 in cervical cancer cell lines. Conclusion The high expression of ALDH1A1 and the low expression of miR-140 may be closely related to the occurrence and development of cervical cancer.miR-140 targets ALDH1A1 and inhibits its expression.This reveals the important role of ALDH1A1 and miR-140 in the occurrence and development of cervical cancer.
[1] Ferlay J,Colombet M,Soerjomataram I,et al.Cancer stati-stics for the year 2020:an overview[J].International Jou-rnal of Cancer,2021.
[2] Wei Y,Li Y,Chen Y,et al.ALDH1:A potential thera-peutic target for cancer stem cells in solid tumors.Front.Oncol.2022,12:1026278.
[3] Hill M,Tran N.miRNA interplay: mechanisms and cons-equences in cancer[J].Disease Models and Mechanisms,2021,14(4).
[4] Tanya B,Troup D B,Wilhite S E,et al.NCBI GEO:min-ing tens of millions of expression profiles—database and tools update[J].Nucleic Acids Research,2007,35(Database issue):D760-5.
[5] Wang X L,Wang S,Wu Z Z,et al.Overexpression of ATAD2 indicates Poor Prognosis in Oral Squamous Cell Carcinoma[J].International Journal of Medical Sc-iences,2020,17(11):1598-1609.
[6] yuemaier,reziwanguli.Upregulation of stem cell markers ALDH1A1 and OCT4 as potential biomarkers for the early detection of cervical carcinoma[C]//2019年中国肿瘤标志物学术大会暨第十三届肿瘤标志物青年科学家论坛论文集. 2019.
[7] Organista-Nava J,Yazmín Gómez-Gómez,Garibay O L,et al.2019.Cervical cancer stem cellassociated genes Prognostic implications in cervical cancer(Review)[J].Oncology letters,2019,18:7-14.
[8] Ciccone V,Terzuoli E,Donnini S,et al.Correction to: Stemness marker ALDH1A1 promotes tumor angio-genesis via retinoic acid/HIF-1α/VEGF signalling in MCF-7 breast cancer cells[J].Journal of Experimental & Clinical Cancer Research,2019,38(1).
[9] Wei Wang,Shujin He,Renya Zhang,et al.ALDH1A1 mai-ntains the cancer stem-like cells properties of esoph-ageal squamous cell carcinoma by activating the AKT signal pathway and interacting with β-catenin[J].Biomedicine & Pharmacotherapy,2020,125:109940.
[10] Correia,Nádia C,Melão,Alice,Póvoa,Vanda,et al.micro-RNAs regulate TAL1 expression in T-cell acute lym-phoblastic leukemia[J].Oncotarget,2016,7(7).
[11] Liu L,Liu Y,Xia Y,et al.Synergistic killing effects of PD-L1-CAR T cells and colorectal cancer stem cell-dendritic cell vaccine-sensitized T cells in ALDH1-positive colorectal cancer stem cells[J].J Cancer,2021,12(22): 6629-6639.
2025, Vol. 45 
