|Table of Contents|

let-7b-3p targeting and regulating ANKRD49 inhibits the invasion and migration of nasopharyngeal carcinoma cells

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 22
Page:
4097-4104
Research Field:
Publishing date:

Info

Title:
let-7b-3p targeting and regulating ANKRD49 inhibits the invasion and migration of nasopharyngeal carcinoma cells
Author(s):
WANG YiGOU XiaoxiaZHU LinHUANG GangCHEN NianZHOU KaiSHEN Shasha
Department of Head and Neck Oncology,the Second Affiliated Hospital of Zunyi Medical University,Guizhou Zunyi 563003,China.
Keywords:
let-7b-3pANKRD49nasopharyngeal carcinomainvasionmigration
PACS:
R739.63
DOI:
10.3969/j.issn.1672-4992.2023.22.001
Abstract:
Objective:To explore the potential mechanism by which let-7b-3p regulates the expression of ankyrin repeat domain 49 (ANKRD49) and affects the invasion and migration of nasopharyngeal carcinoma (NPC) cells.Methods:GEO and TCGA databases were used to analyze the expression level of let-7b in NPC and head and neck tumor tissues and its relationship with clinicopathological parameters.The expression level of ANKRD49 in NPC and nasopharyngeal inflammatory tissues was detected by immunohistochemical technique.RT-PCR detected let-7b-3p expression in NPC cell lines.Transwell invasion assay and scratch assay were used to detect the role of let-7b-3p in the invasion and migration of NPC cells.The targeting relationship between let-7b-3p and ANKRD49 was verified by dual luciferase gene reporter assay.RT-PCR,Western Blot and reply experiments verified the regulatory effect of let-7b-3p on ANKRD49.Results:Based on NPC miRNA microarray analysis,let-7b-3p expression was down-regulated in NPC tissues compared with normal nasopharyngeal tissues,and the expression level of let-7b-3p was correlated with tumor invasion depth and lymph node stage (P<0.05).Immunohistochemistry showed that ANKRD49 was highly expressed in NPC tissues.The results of invasion and migration experiments showed that the let-7b-3p mimic group and the inhibitor group respectively inhibited and promoted the invasion ability and migration ability of NPC cells (both P<0.05).The double-luciferase reporter assay showed that let-7b-3p mimic could inhibit the luciferase activity of ANKRD49-wt (0.35±0.08 vs 0.61±0.05,P<0.01),but did not affect the luciferase activity of ANKRD49-mut (0.64±0.13 vs 0.57±0.13,P>0.05).The results of RT-PCR and Western Blot showed that the expression levels of ANKRD49 mRNA and protein in the let-7b-3p inhibitor group were higher than those in the normal group and let-7b-3p mimic group.Reversion experiments found that interference with ANKRD49 affects the promoting and inhibiting effects of let-7b-3p inhibitor group and let-7b-3p mimic group on the invasion and migration of NPC cells.Conclusion:let-7b-3p regulates the expression of ANKRD49 to inhibit the invasion and migration of NPC cells.The let-7b-3p/ANKRD49 axis may be a potential therapeutic target for NPC.

References:

[1]LIU GY,LI WZ,WANG DS,et al.Effect of capecitabine maintenance therapy plus best supportive care vs best supportive care alone on progression-free survival among patients with newly diagnosed metastatic nasopharyngeal carcinoma who had received induction chemotherapy:A phase 3 randomized clinical trial[J].JAMA Oncology,2022,8(4):553-561.
[2]PENG Z,WANG Y,FAN R,et al.Treatment of recurrent nasopharyngeal carcinoma:A sequential challenge[J].Cancers,2022,14(17):4111.
[3]MENON A,ABD-AZIZ N,KHALID K,et al.miRNA:A promising therapeutic target in cancer[J].International Journal of Molecular Sciences,2022,23(19):11502.
[4]MARTINS CSM,LAGROW AP,PRIOR JAV.Quantum dots for cancer-related miRNA monitoring[J].ACS Sensors,2022,7(5):1269-1299.
[5]TSAI YS,HUANG CI,TSAI PC,et al.Circulating Let-7 family members as non-invasive biomarkers for predicting hepatocellular carcinoma risk after antiviral treatment among chronic hepatitis C patients[J].Cancers,2022,14(8):2023.
[6]ZHANG X,YIN Z,LI C,et al.KDM2B mediates the Wnt/β-catenin pathway through transcriptional activation of PKMYT1 via microRNA-let-7b-5p/EZH2 to affect the development of non-small cell lung cancer[J].Experimental Cell Research,2022,417(2):113208.
[7]LIRUSSI L,AYYILDIZ D,LIU Y,et al.A regulatory network comprising let-7 miRNA and SMUG1 is associated with good prognosis in ER+ breast tumours[J].Nucleic Acids Research,2022,50(18):10449-10468.
[8]YU D,LIU X,HAN G,et al.The let-7 family of microRNAs suppresses immune evasion in head and neck squamous cell carcinoma by promoting PD-L1 degradation[J].Cell Communication and Signaling,2019,17(1):173.
[9]LI Y,DONG R,LU M,et al.Let-7b-3p inhibits tumor growth and metastasis by targeting the BRF2-mediated MAPK/ERK pathway in human lung adenocarcinoma[J].Translational Lung Cancer Research,2021,10(4):1841-1856.
[10]宋伟国,钱莉莉,吴大保,等.宫颈癌细胞中ΔNp63α的MicroRNA表达谱及其对hsa-let-7b-3p的调控机制[J].肿瘤防治研究,2018,45(03):138-143. SONG WG,QIAN LL,WU DB,et al.MicroRNA expression profile of ΔNp63α in cervical cancer cells and its regulation mechanism on hsa-let-7b-3p[J].Tumor Prevention and Treatment Research,2018,45(03):138-143.
[11]LIN M,ZHANG XL,YOU R,et al.Evolutionary route of nasopharyngeal carcinoma metastasis and its clinical significance[J].Nature Communications,2023,14(1):610.
[12]ADKINS DR,HADDAD RI.Clinical trial data of anti-PD-1/PD-L1 therapy for recurrent or metastatic nasopharyngeal carcinoma:A review[J].Cancer Treatment Reviews,2022,109:102428.
[13]WANG S,SUN Z,LEI Z,et al.RNA-binding proteins and cancer metastasis[J].Seminars in Cancer Biology,2022,86(Pt 2):748-768.
[14]MO Y,WANG Y,WANG Y,et al.Circular RNA circPVT1 promotes nasopharyngeal carcinoma metastasis via the β-TrCP/c-Myc/SRSF1 positive feedback loop[J].Molecular Cancer,2022,21(1):192.
[15]LUO H,ZHONG F,JING X,et al.miRNA profiling of human nasopharyngeal carcinoma cell lines HONE1 and CNE2 after X-ray therapy[J].Advances in Clinical and Experimental Medicine:Official Organ Wroclaw Medical University,2022,31(6):671-687.
[16]GONG Y,JIANG Q,LIU L,et al.METTL3-mediated m6A modification promotes processing and maturation of pri-miRNA-19a to facilitate nasopharyngeal carcinoma cell proliferation and invasion[J].Physiological Genomics,2022,54(9):337-349.
[17]谢辰,姚梦纤,曹忠胜,等.miR-409-3p靶向调控RRM2抑制鼻咽癌细胞增殖、迁移及侵袭[J].现代肿瘤医学,2021,29(6):912-918. XIE C,YAO MX,CAO ZS,et al.miR-409-3p inhibits proliferation,migration and invasion of nasopharyngeal carcinoma cells by targeted regulation of RRM2[J].Modern Oncology,2021,29(6):912-918.
[18]谭建成,刘鑫国,邢金燕.miR-429在鼻咽癌细胞中的表达及其对细胞增殖、迁移的影响[J].现代肿瘤医学,2021,29(9):1501-1506. TAN JC,LIU XG,XING JY.The expression of miR-429 in nasopharyngeal carcinoma cells and its effects on cell proliferation and migration[J].Modern Oncology,2021,29(9):1501-1506.
[19]LEE RC,FEINBAUM RL,AMBROS V.The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14[J].Cell,1993,75(5):843-854.
[20]YOU B,ZHANG P,GU M,et al.Let-7i-5p promotes a malignant phenotype in nasopharyngeal carcinoma via inhibiting tumor-suppressive autophagy[J].Cancer Letters,2022,531:14-26.
[21]WU A,WU K,LI J,et al.Let-7a inhibits migration, invasion and epithelial-mesenchymal transition by targeting HMGA2 in nasopharyngeal carcinoma[J].Journal of Translational Medicine,2015,13:105.
[22]CHOPRA M,MCENTAGART M,CLAYTON-SMITH J,et al.Heterozygous ANKRD17 loss-of-function variants cause a syndrome with intellectual disability,speech delay,and dysmorphism[J].American Journal of Human Genetics,2021,108(6):1138-1150.
[23]LI XY,QIN KR,LIU YH,et al.A microarray study on the expression of ANKRD49 in lung squamous cell carcinoma and its clinicopathologic significance[J].Applied Immunohistochemistry & Molecular Morphology,2022,30(6):418-424.
[24]CHRISTENSEN T,JENSEN L,BOUZINOVA EV,et al.Molecular profiling of the lateral habenula in a rat model of depression[J].PLoS One,2013,8(12):e80666.
[25]LIU YH,YUAN M,XU BX,et al.ANKRD49 promotes the invasion and metastasis of lung adenocarcinoma via a P38/ATF-2 signalling pathway[J].Journal of Cellular and Molecular Medicine,2022,26(16):4401-4415.
[26]LIU CG,CUI XL,WEI ZG,et al.High expression of the ANKRD49 protein is associated with progression and poor prognosis of gastric cancer[J].Cancer Biomarkers:Section A of Disease Markers,2018,22(4):649-656.
[27]NAKAJIMA R,ZHAO L,ZHOU Y,et al.Deregulated E2F activity as a cancer-cell specific therapeutic tool[J].Genes,2023,14(2):393.
[28]KASSAB A,GUPTA I,MOUSTAFA AE.Role of E2F transcription factor in oral cancer:Recent insight and advancements[J].Seminars in Cancer Biology,2023,92:28-41.
[29]BARCZAK W,JIN L,CARR SM,et al.PRMT5 promotes cancer cell migration and invasion through the E2F pathway[J].Cell Death & Disease,2020,11(7):572.
[30]JING C,DUAN Y,ZHOU M,et al.Blockade of deubiquitinating enzyme PSMD14 overcomes chemoresistance in head and neck squamous cell carcinoma by antagonizing E2F1/Akt/SOX2-mediated stemness[J].Theranostics,2021,11(6):2655-2669.

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贵州省卫生健康委科学技术基金项目(编号:gzwkj2021-053);贵州省科技厅基础研究计划[编号:黔科合基础-ZK(2023)一般525];贵州省遵义市科技厅项目[编号:遵市科合HZ字(2022)407号]
Last Update: 1900-01-01