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XPD inhibits cell growth and invasion and enhances chemosensitivity in esophageal squamous cell carcinoma by regulating the PI3K/AKT signaling pathway.

ABSTRACT: Esophageal squamous cell carcinoma (ESCC) is a lethal disease due to its high aggressiveness. The aim of the present study was to investigate the role of xeroderma pigmentosum complementation group D (XPD) in the growth and invasion of ESCC and to elucidate the potential underlying molecular mechanisms. Western blot analysis and RT?qPCR were used to detect the expression level of XPD in ESCC tissue samples and adjacent normal esophageal tissue samples. The pEGFP?N2/XPD plasmid was transfected into human ESCC cell lines (EC9706 and EC109). The proliferation, apoptosis, migration and invasion of EC9706 or EC109 cells were assessed following transfection with the XPD overexpression plasmid. The chemosensitivity of EC9706 or EC109 cells to cisplatin or fluorouracil was evaluated by CCK?8 assay. The expression levels of phosphoinositide 3?kinase (PI3K)/AKT, nuclear factor (NF)??B, Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) and mitogen?activated protein kinase (MAPK) signaling pathway?related genes were detected by RT?qPCR and western blot analysis. The results demonstrated that the expression level of XPD was markedly lower in ESCC tissue samples than in adjacent normal esophageal tissue samples. The pEGFP?N2/XPD plasmid was successfully transfected into EC9706 or EC109 cells, inducing XPD overexpression. A High XPD expression markedly suppressed cell proliferation, migration and invasion, and increased the apoptotic rate of EC9706 and EC109 cells. Furthermore, the overexpression of XPD significantly increased the chemosensitivity of EC9706 and EC109 cells to cisplatin or fluorouracil. Following XPD overexpression, the expression levels of PI3K, p?AKT, c?Myc, Cyclin D1, Bcl?2, vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)?9 were markedly downregulated, while the expression level of p21 was markedly upregulated. On the whole, the findings of the present study demonstrate that XPD inhibits the growth and invasion of EC9706 and EC109 cells, whilst also enhancing the chemosensitivity of EC9706 and EC109 cells to cisplatin or fluorouracil by regulating the PI3K/AKT signaling pathway. XPD may thus be an underlying target for ESCC treatment and drug resistance.

SUBMITTER: Jian J

PROVIDER: S-EPMC7255471 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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XPD inhibits cell growth and invasion and enhances chemosensitivity in esophageal squamous cell carcinoma by regulating the PI3K/AKT signaling pathway.

Jian Jie J Li Shuang S Liu Li-Zhen LZ Zhen Li L Yao Ling L Gan Li-Hong LH Huang Ya-Qing YQ Fang Nian N

International journal of molecular medicine 20200504 1

Esophageal squamous cell carcinoma (ESCC) is a lethal disease due to its high aggressiveness. The aim of the present study was to investigate the role of xeroderma pigmentosum complementation group D (XPD) in the growth and invasion of ESCC and to elucidate the potential underlying molecular mechanisms. Western blot analysis and RT‑qPCR were used to detect the expression level of XPD in ESCC tissue samples and adjacent normal esophageal tissue samples. The pEGFP‑N2/XPD plasmid was transfected in ...[more]

PMID: 32377720

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Project description:PurposeMicroRNAs dysregulation has been confirmed in multiple malignancies. This paper reported the molecular mechanism of miR-204-5p in esophageal squamous cell carcinoma (ESCC).MethodsmiR-204-5p expression in 30 ESCC tumor tissues and 10 normal tissues was downloaded from RNA-seq data. ESCC tissues/normal tissues of 97 ESCC patients were collected. TE-1 and KYSE510 cells were transfected by miR-204-5p mimic, inhibitor, siYWHAZ or their corresponding controls. The phenotype of cells was detected by CCK-8 assay, transwell experiment, and flow cytometry. Luciferase reporter gene assay and RNA-binding protein immunoprecipitation (RIP) were performed to verify the targeting relationship between miR-204-5p and YWHAZ. miR-204-5p and YWHAZ expression in tissues/cells was detected by qRT-PCR and Western blot. Xenograft tumor experiment was performed.ResultsmiR-204-5p expression was declined in ESCC patients and cells, which was indicated the poor outcome of patients. Compared with siNC group, TE-1 cells in miR-204-5p inhibitor group had higher OD450 value, less cell percentage in G1 phase, and more cell percentage in S phase, lower apoptosis percentage, and higher migration and invasion cell numbers. Moreover, KYSE510 cells of miR-204-5p mimic group showed lower OD450 value, more cell percentage in G1 phase and less cell percentage in S phase, higher apoptosis percentage, and lower migration and invasion cell numbers than control. YWHAZ was directly inhibited by miR-204-5p. Relative to siNC group, TE-1 cells of miR-inhibitor group exhibited higher YWHAZ protein expression, higher OD450 value, less cell percentage in G1 phase and more cell percentage in S phase, lower apoptosis percentage, higher migration and invasion cell numbers, and higher p-PI3K/PI3K and p-AKT/AKT protein expression, while siYWHAZ rescued the effects of miR-inhibitor. miR-204-5p up-regulation inhibited ESCC growth in vivo.ConclusionmiR-204-5p inhibits ESCC progression by targeted inhibition of YWHAZ/PI3K/AKT.

Dataset Information

XPD inhibits cell growth and invasion and enhances chemosensitivity in esophageal squamous cell carcinoma by regulating the PI3K/AKT signaling pathway.

Publications

XPD inhibits cell growth and invasion and enhances chemosensitivity in esophageal squamous cell carcinoma by regulating the PI3K/AKT signaling pathway.

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