|Table of Contents|

miR-623 regulates esophageal squamous cell carcinoma cell proliferation,migration and invasion by targeting MMP1

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

Issue:
2024 14
Page:
2511-2517
Research Field:
Publishing date:

Info

Title:
miR-623 regulates esophageal squamous cell carcinoma cell proliferation,migration and invasion by targeting MMP1
Author(s):
FEI Song; WU Weidong; LI Dan; FANG Mingxing; JIN Bo
Department of Cardio-Thoracic Surgery，Guangzhou Red Cross Hospital of Jinan University，Guangdong Guangzhou 510220，China.
Keywords:
esophageal squamous cell carcinoma; miR-623; MMP1; proliferation; apoptosis; migration; invasion
PACS:
R735.1
DOI:
10.3969/j.issn.1672-4992.2024.14.003
Abstract:
Objective:To analyze the expression level of matrix metalloproteinase 1 (MMP1) in esophageal squamous cell carcinoma tissues,and explore the molecular mechanism that miRNA-623 (miR-623) targets MMP1 affecting the proliferation,migration,invasion and apoptotic ability of esophageal squamous cell carcinoma cells.Methods:The microarray database on esophageal squamous cell carcinoma was downloaded from the GEO database,and 53 pairs of esophageal squamous cell carcinoma and paracancerous tissues were analyzed for the expression level of MMP1 mRNA.qRT-PCR and Western blot were used to detect the expression level of miR-623 and MMP1 protein in human normal esophageal squamous epithelial cells (HET-1A) and human esophageal squamous cell carcinoma cell lines (TE-10,KYSE30,KYSE180).Bioinformatics method was used to analyze the target sequences of miR-623 binding to MMP1.Dual luciferase reporter gene assay was performed to detect the targeting and regulatory mechanism of miR-623 on MMP1.The miR-623 mimic was transfected into TE-10 esophageal squamous cell carcinoma cell line by liposome assay,and the expression level of MMP1 in TE-10 cell line was detected by qRT-PCR and Western blot.The cell proliferation ability was observed by CCK-8 assay.The cell apoptosis ability was observed by flow cytometry,and the cell migration and invasion ability was observed by cell scratch assay and Transwell invasion assay.Results:The average expression of MMP1 mRNA in esophageal squamous cell carcinoma tissues was significantly higher than that in paracancerous tissues (P＜0.05).Compared with human normal esophageal squamous epithelial cell line,the expression level of miR-623 was significantly down-regulated in esophageal squamous cell carcinoma cell lines (P＜0.05),while the protein level of MMP1 was clearly up-regulated (P＜0.05).Dual luciferase reporter gene assay showed that miR-623 significantly affected the luciferase activity of MMP1 3'-UTR expression vector (P＜0.05).Overexpression of miR-623 significantly inhibited the MMP1 expression level,cell proliferation,migration and invasion ability of esophageal squamous carcinoma cell lines,and promoted cell apoptosis (all P＜0.05).Conclusion:In esophageal squamous cell carcinoma,miR-623 was lowly expressed and MMP1 was highly expressed.miR-623 could target and regulate the expression of oncogene MMP1,thus regulating the proliferation,apoptosis,migration and invasion of esophageal squamous cell carcinoma cells,suggesting that miR-623 may be a potential therapeutic target for esophageal squamous cell carcinoma.

References:

[1]FERLAY J,COLOMBET M,SOERJOMATARAM I,et al.Cancer statistics for the year 2020:An overview［J］.International Journal of Cancer,2021,149(4):778-789.
[2]LIANG H,FAN JH,QIAO YL.Epidemiology,etiology,and prevention of esophageal squamous cell carcinoma in China［J］.Cancer Biology & Medicine,2017,14(1):33-41.
[3]ABDEL-HAMID NM,ABASS SA.Matrix metalloproteinase contribution in management of cancer proliferation,metastasis and drug targeting［J］.Molecular Biology Reports,2021,48(9):6525-6538.
[4]CABRAL-PACHECO GA,GARZA-VELOZ I,CASTRUITA-DE LA ROSA C,et al.The roles of matrix metalloproteinases and their inhibitors in human diseases［J］.International Journal of Molecular Sciences,2020,21(24):E9739.
[5]吴伟东,侯文进,刘丹,等.MMP-3、MMP-9和TIMP-1的动态平衡可作为心肌基质重构的重要标志［J］.分子影像学杂志,2015,38(02):84-88. WU WD,HOU WJ,LIU D,et al.The homeostasis of MMP-3,MMP-9 and TIMP-1 can be used as an important sign of myocardial matrix reconstruction［J］.Journal of Molecular Imaging,2015,38(02):84-88.
[6]刘清峰,吴伟东,古佳升,等.肿瘤标志物ESM-1 MMP-2和MMP-9鉴别良恶性胸腔积液的临床意义［J］.中国临床新医学,2021,14(10):1027-1031. LIU QF,WU WD,GU JS,et al.Clinical significance of tumor markers ESM-1,MMP-2 and MMP-9 in identifying benign and malignant pleural effusions［J］.Chinese Journal of New Clinical Medicine,2021,14(10):1027-1031.
[7]JONSSON A,FALK P,ANGENETE E,et al.Plasma MMP-1 expression as a prognostic factor in colon cancer［J］.Journal of Surgical Research,2021,266:254-260.
[8]KURNIA I,RAUF S,HATTA M,et al.Molecular patho-mechanisms of cervical cancer (MMP1)［J］.Annals of Medicine and Surgery,2022,77:103415.
[9]WEI X,ZHANG B,PAN B.MMP1 is a prognostic-related biomarker and correlated with immune infiltration in breast cancer［J］.Health,2022,14(02):219.
[10]MING XY,ZHANG X,CAO TT,et al.RHCG suppresses tumorigenicity and metastasis in esophageal squamous cell carcinoma via inhibiting NF-κB signaling and MMP1 expression［J］.Theranostics,2018,8(1):185-198.
[11]ZOU S,YANG J,GUO J,et al.RAD18 promotes the migration and invasion of esophageal squamous cell cancer via the JNK-MMPs pathway［J］.Cancer Letters,2018,417:65-74.
[12]REN F,SU H,JIANG H,et al.Overexpression of miR-623 suppresses progression of hepatocellular carcinoma via regulating the PI3K/Akt signaling pathway by targeting XRCC5［J］.Journal of Cellular Biochemistry,2020,121(1):213-223.
[13]LI Q,LIU J,JIA Y,et al.miR-623 suppresses cell proliferation,migration and invasion through direct inhibition of XRCC5 in breast cancer［J］.Aging,2020,12(11):10246-10258.
[14]HAMMASH D,MAHFOOD M,KHODER G,et al.miR-623 targets metalloproteinase-1 and attenuates extravasation of brain metastatic triple-negative breast cancer cells［J］.Breast Cancer (Dove Medical Press),2022,14:187-198.
[15]CHEN Y,PENG S,CEN H,et al.MicroRNA hsa-miR-623 directly suppresses MMP1 and attenuates IL-8-induced metastasis in pancreatic cancer［J］.International Journal of Oncology,2019,55(1):142-156.
[16]SU H,HU N,YANG HH,et al.Global gene expression profiling and validation in esophageal squamous cell carcinoma and its association with clinical phenotypes［J］.Clinical Cancer Research,2011,17(9):2955-2966.
[17]CHEN YK,TUNG CW,LEE JY,et al.Plasma matrix metalloproteinase 1 improves the detection and survival prediction of esophageal squamous cell carcinoma［J］.Scientific Reports,2016,6:30057.
[18]LIU M,HU Y,ZHANG MF,et al.MMP1 promotes tumor growth and metastasis in esophageal squamous cell carcinoma［J］.Cancer Letters,2016,377(1):97-104.
[19]BOIRE A,COVIC L,AGARWAL A,et al.PAR1 is a matrix metalloprotease-1 receptor that promotes invasion and tumorigenesis of breast cancer cells［J］.Cell,2005,120(3):303-313.
[20]JUNCKER-JENSEN A,DERYUGINA E I,RIMANN I,et al.Tumor MMP-1 activates endothelial PAR1 to facilitate vascular intravasation and metastatic dissemination［J］.Cancer Research,2013,73(14):4196-4211.
[21]SAITO R,MIKI Y,ISHIDA N,et al.The significance of MMP-1 in EGFR-TKI-resistant lung adenocarcinoma:potential for therapeutic targeting［J］.International Journal of Molecular Sciences,2018,19(2):E609.
[22]KIM HW,PARK JE,BAEK M,et al.Matrix metalloproteinase-1 (MMP1) upregulation through promoter hypomethylation enhances tamoxifen resistance in breast cancer［J］.Cancers,2022,14(5):1232.
[23]SONG L,LIU H,LIU Q.Matrix metalloproteinase 1 promotes tumorigenesis and inhibits the sensitivity to 5-fluorouracil of nasopharyngeal carcinoma［J］.Biomedicine & Pharmacotherapy,2019,118:109120.
[24]ZHOU H,XIANG Q,HU C,et al.Identification of MMP1 as a potential gene conferring erlotinib resistance in non-small cell lung cancer based on bioinformatics analyses［J］.Hereditas,2020,157(1):32.
[25]陆艳荣,巴尔夏古丽·扎比胡拉,王海峰.血清微小RNA-623和微小RNA-5703及微小RNA-483-5p与局部晚期食管鳞癌患者新辅助放化疗效果的关系［J］.中国医药,2021,16(2):245-249. LU YR,BALSHAGURI ZABIHULA,WANG HF.Relationship between serum microRNA-623 and microRNA-5703 and microRNA-483-5p and the effect of neoadjuvant radiotherapy in patients with locally advanced esophageal squamous carcinoma［J］.Chinese Medicine,2021,16(2):245-249.
[26]张建清.预测新疆不同民族局部晚期食管鳞癌放化疗疗效的血清microRNA初步筛选［D］.乌鲁木齐:新疆医科大学,2017. ZHANG JQ.Preliminary screening of serum microRNAs for predicting the efficacy of radiotherapy for locally advanced esophageal squamous carcinoma in different ethnic groups in Xinjiang［D］.Urumchi:Xinjiang Medical University,2017.
[27]CUI D,WANG K,LIU Y,et al.MicroRNA-623 inhibits epithelial-mesenchymal transition to attenuate glioma proliferation by targeting TRIM44［J］.OncoTargets and Therapy,2020,13:9291-9303.
[28]JIANG L,YANG W,BIAN W,et al.MicroRNA-623 targets Cyclin D1 to inhibit cell proliferation and enhance the chemosensitivity of cells to 5-fluorouracil in gastric cancer［J］.Oncology Research,2018,27(1):19-27.

Memo

Memo:
广东省广州市科技计划项目（编号：201902010003）
Last Update: 1900-01-01