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Low-Dose Radiation Promotes Invasion and Migration of A549 Cells by Activating the CXCL1/NF-?B Signaling Pathway.

ABSTRACT: Purpose:Radiation has well-known and well-characterized direct toxic effects on cells and tissues. However, low-dose ionizing irradiation (LDIR) can also enhance the invasion and migration of tumor cells, and the mechanisms underlying these effects remain unclear. The present study aimed to investigate changes induced in the migration and invasion of A549 cells after LDIR and to explore the potential molecular mechanism. Materials and Methods:A549 cells were irradiated with X-rays at different doses (0, 2, 4, and 6 Gy) and cultured for 24 or 48 h. Apoptosis and proliferation were evaluated by lactate dehydrogenase release, CCK8, colony formation, and flow cytometry assays. Wound-healing and transwell assays were performed to detect migration and invasion ability. CXCL1 or p65 were knocked down using lentivirus-mediated siRNA in A549 cell lines. Knockdown efficiency of CXCL1 and p65 was assessed by RT-qPCR. Western blotting and immunofluorescence were used to determine the changes in protein levels. Results:In cells irradiated with a dose of 6 Gy, after 48 h, apoptosis was clearly induced while proliferation was inhibited. Irradiation with 4 Gy resulted in the upregulation of CXCL1 expression and activation of the NF-?B signaling pathway. Moreover, upon 4 Gy irradiation, migration, invasion, and epithelial-mesenchymal transition (EMT) were significantly enhanced in A549 cells. Importantly, CXCL1 or p65 knockdown inhibited radiation-induced migration, invasion, and EMT. Conclusion:Low-dose radiation upregulates CXCL1 expression and activates the NF-?B signaling to regulate EMT in A549 cells, thereby promoting invasion and migration. These results provide new insights into the prevention of tumor invasion and metastasis induced by radiotherapy.

SUBMITTER: Li J

PROVIDER: S-EPMC7197943 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Low-Dose Radiation Promotes Invasion and Migration of A549 Cells by Activating the CXCL1/NF-κB Signaling Pathway.

Li Jing J Wu Dong-Ming DM Han Rong R Yu Ye Y Deng Shi-Hua SH Liu Teng T Zhang Ting T Xu Ying Y

OncoTargets and therapy 20200429

<h4>Purpose</h4>Radiation has well-known and well-characterized direct toxic effects on cells and tissues. However, low-dose ionizing irradiation (LDIR) can also enhance the invasion and migration of tumor cells, and the mechanisms underlying these effects remain unclear. The present study aimed to investigate changes induced in the migration and invasion of A549 cells after LDIR and to explore the potential molecular mechanism.<h4>Materials and methods</h4>A549 cells were irradiated with X-rays ...[more]

PMID: 32431513

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Project description:Objective:Breast cancer has become the most common malignancy among women worldwide; therefore, novel diagnostic and prognostic markers and therapeutic targets are urgently required. NF-?B signaling plays a pivotal role in enhancing breast cancer malignant phenotypes, especially cancer invasion and metastasis, which is the main cause of death in cancer patients. TNIP2, an important inhibitor of the NF-?B pathway, is known to involve a negative feedback loop of the NF-?B signaling cascade and to regulate tumor aggressiveness in various cancer types. However, the mRNA level of TNIP2 is barely altered in breast cancer; thus, the mechanism that regulates TNIP2 in breast cancer still needs to be elucidated. Methods:We analyzed the expression and prognosis of miR-423 in a TCGA BRCA miRNA cohort and in clinical specimens. We detected the invasive capacity through a Matrigel-coated Transwell penetration assay, a three-dimensional (3D) spheroid invasion assay and a wound healing assay. Then, we applied luciferase assays, real-time PCR assays and Western blotting to further study the mechanism. Results:In this study, analysis of the TCGA BRCA miRNA cohort and clinical specimens demonstrated that miR-423 was upregulated in human breast cancers and was positively correlated with clinical stage, poor overall survival and metastasis classification. Moreover, the invasiveness of breast cancer cells was enhanced by ectopic expression of miR-423 and inhibited by miR-423 downregulation. Mechanistically, upregulation of miR-423 led to activation of the NF-?B signaling pathway and elevated expression of snail and twist, while repression of miR-423 inhibited this pathway. Furthermore, the results indicated that TNIP2 is a target gene of miR-423, and suppression of TNIP2 resulted in increased invasiveness in miR-423-silenced cells. Conclusion:Our results suggest that miR-423 is a crucial factor that enhances breast cancer cell invasion through the NF-?B signaling pathway and shed light on miR-423 as a promising prognostic and therapeutic marker for metastatic breast cancer.

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Low-Dose Radiation Promotes Invasion and Migration of A549 Cells by Activating the CXCL1/NF-?B Signaling Pathway.

Publications

Low-Dose Radiation Promotes Invasion and Migration of A549 Cells by Activating the CXCL1/NF-κB Signaling Pathway.

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