ATM‑JAK‑PD‑L1 signaling pathway inhibition decreases EMT and metastasis of androgen‑independent prostate cancer

Zhang, Lan; Xu, Lanfang; Zhu, Jin; Li, Jian; Xue, Boxin; Gao, Jie; Sun, Chuanyu; Zang, Yu‐Feng; Zhou, Yibin; Yang, Dian; Shan, Yuxi

doi:10.3892/mmr.2018.8781

Cited by 20 publications

(26 citation statements)

References 46 publications

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“…They discovered that polyphyllin I, a natural compound, can reverse EMT by regulating the IL-6/STAT3 signaling pathway in non–small cell lung cancer [25]. Moreover, Zhang et al have determined that EMT can be regulated in prostate cancer by the ataxia telangiectasia-mutated ( ATM ) protein kinase/STAT3/PD-L1 signaling pathway and that PD-L1 is significantly reduced when ATM is knocked down [26]. Asgarova et al also observed upregulated PD-L1 during EMT and described tumor cells' increased proliferation, infiltration, and migration capacities and greater ability to escape immune system detection during EMT [27].…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Indoleamine 2,3-Dioxygenase 1 Promotes Epithelial-Mesenchymal Transition by Activation of the IL-6/STAT3/PD-L1 Pathway in Bladder Cancer

Zhang

et al. 2019

Translational Oncology

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Indoleamine 2,3-dioxygenase 1 (IDO1) is a key enzyme in tryptophan metabolism and plays an important role in tumor cell immunosuppression and angiogenesis. The molecular mechanisms of IDO1 and epithelial-mesenchymal transition (EMT) have not been elucidated or studied in bladder cancer. Therefore, the aims of this study were to detect IDO1 expression in bladder cancer tissues and then to investigate the role of IDO1 in bladder cancer cell EMT and malignant phenotypes as well as the underlying molecular mechanisms. By immunohistochemistry, Western blot, and quantitative reverse transcription–polymerase chain reaction experiments, IDO1 was found to be overexpressed in bladder cancer tissues and cell lines compared to the noncancerous ones. In addition, knockdown of IDO1 expression was shown to inhibit bladder cancer cell growth, migration, invasion, and EMT. Furthermore, we demonstrated that IDO1 may promote EMT by activation of the interleukin 6/signal transducer and activator of transcription 3/programmed cell death ligand 1 signaling pathway. Collectively, these data suggest that IDO1 may play an important role in bladder cancer and may be a novel therapeutic target for patients with bladder cancer.

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Section: Discussionmentioning

confidence: 99%

Overexpression of Indoleamine 2,3-Dioxygenase 1 Promotes Epithelial-Mesenchymal Transition by Activation of the IL-6/STAT3/PD-L1 Pathway in Bladder Cancer

Zhang

et al. 2019

Translational Oncology

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“…Another study reported that the ATM inhibitor KU-55933 can hinder cancer cell proliferation by inducing G1 blockade and thereby triggering apoptosis in cancer cells [39]. Liu R et al also revealed that ATM deletion could dramatically decrease the proliferation, migration and invasion of colon cancer cells [40], which could also lead to a remarkable reduction in migration and epithelial-mesenchymal transition (EMT) in prostate cancer cells [41]. In our experiment, ATM was confirmed to be the downstream target gene of miR-203a-3p through bioinformatics prediction and a dual-luciferase reporter gene assay.…”

Section: Discussionmentioning

confidence: 99%

MiR-203a-3p regulates the biological behaviors of ovarian cancer cells through mediating the Akt/GSK-3β/Snail signaling pathway by targeting ATM

et al. 2019

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Objective To investigate whether miR-203a-3p can regulate the biological behaviors of ovarian cancer cells by targeting ATM to affect the Akt/GSK-3β/Snail signaling pathway. Methods The expression levels of miR-203a-3p and ATM were detected by qRT-PCR, immunohistochemical staining and Western blotting in ovarian cancer tissues and adjacent normal tissues obtained from 152 subjects. A dual-luciferase reporter gene assay was performed to verify the relationship between miR-203a-3p and ATM. Human ovarian cancer cell lines (A2780 and SKOV3) were used to generate the Blank, miR-NC, miR-203a-3p mimic, Control siRNA, ATM siRNA, and miR-203a-3p inhibitor + ATM siRNA groups. The biological behaviors of ovarian cancer cells were evaluated by CCK-8, wound healing, and Transwell invasion assays, annexin V-FITC/PI staining and flow cytometry. The levels of Akt/GSK-3β/Snail pathway-related proteins were assessed by Western blotting. Results Ovarian cancer tissues showed lower miR-203a-3p levels and higher ATM levels than adjacent normal tissues, both of which were associated with the FIGO stage, grade and prognosis of ovarian cancer. As confirmed by a dual-luciferase reporter gene assay, miR-203a-3p could target ATM . Furthermore, the miR-203a-3p mimic had multiple effects, including the inhibition of the proliferation, invasion and migration of A2780 and SKOV3 cells, the promotion of cell apoptosis, the arrest of the cell cycle at the G1 phase, and the blockage of the Akt/GSK-3β/Snail signaling pathway. ATM siRNA had similar effects on the biological behaviors of ovarian cancer cells, and these effects could be reversed by a miR-203a-3p inhibitor. Conclusion miR-203a-3p was capable of hindering proliferation, migration, and invasion and facilitating the apoptosis of ovarian cancer cells through its modulation of the Akt/GSK-3β/Snail signaling pathway by targeting ATM, and therefore it could serve as a potential therapeutic option for ovarian cancer.

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“…Furthermore, PD‐L1 has been verified to be associated with JAK activation . Intriguingly, ATM‐JAK‐PD‐L1 signaling pathway has been discovered to promote EMT and metastasis of androgen‐independent prostate cancer . In present study, we firstly uncover that SNHG20 modulates the levels of p‐ATM, p‐JAK1/2, and PD‐L1 in ESCC cells.…”

Section: Discussionmentioning

confidence: 65%

Upregulation of long noncoding RNA SNHG20 promotes cell growth and metastasis in esophageal squamous cell carcinoma via modulating ATM‐JAK‐PD‐L1 pathway

Zhang

Jiang

et al. 2019

J of Cellular Biochemistry

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Increasing evidence have proved that long noncoding RNAs (lncRNAs) play significant roles in tumorigenesis and development of various cancers. However, the effect of small nucleolar RNA host gene 20 (SNHG20) on the progression of esophageal squamous cell carcinoma (ESCC) remains to be discovered. Herein, we aim to find out the function and the possible mechanism of SNHG20 in ESCC progression. In our study, we demonstrate that SNHG20 is markedly upregulated in ESCC tissues and cell lines. Besides, the level of SNHG20 is closely associated with tumor size, lymph node metastasis, TNM stage, and tumor grade. In addition, SNHG20 level is an independent predictor for clinical outcomes of ESCC patients. Then the gain-and loss-of-function assays reveal that SNHG20 overexpression promotes cell proliferation, migration, invasion, and epithelialmesenchymal transition as well as represses apoptosis, whereas depletion of SNHG20 exhibits opposite effects. Moreover, we uncover that SNHG20 modulates the expression of ataxia telangiectasia-mutated kinase (p-ATM), p-JAK1/2, and programmed cell death 1 ligand 1 (PD-L1) in ESCC cells and ATM upregulation restores the suppressive effect of SNHG20 inhibition on ESCC progression. Therefore, we conclude that SNHG20 serves as a carcinogen in ESCC by promoting growth and metastasis via ATM-JAK-PD-L1 pathway, supplying a possibly effective therapeutic target for ESCC. K E Y W O R D SATM-JAK-PD-L1 pathway, epithelial-mesenchymal transition, esophageal squamous cell carcinoma, metastasis, proliferation, small nucleolar RNA host gene 20

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ATM‑JAK‑PD‑L1 signaling pathway inhibition decreases EMT and metastasis of androgen‑independent prostate cancer

Cited by 20 publications

References 46 publications

Overexpression of Indoleamine 2,3-Dioxygenase 1 Promotes Epithelial-Mesenchymal Transition by Activation of the IL-6/STAT3/PD-L1 Pathway in Bladder Cancer

Overexpression of Indoleamine 2,3-Dioxygenase 1 Promotes Epithelial-Mesenchymal Transition by Activation of the IL-6/STAT3/PD-L1 Pathway in Bladder Cancer

MiR-203a-3p regulates the biological behaviors of ovarian cancer cells through mediating the Akt/GSK-3β/Snail signaling pathway by targeting ATM

Upregulation of long noncoding RNA SNHG20 promotes cell growth and metastasis in esophageal squamous cell carcinoma via modulating ATM‐JAK‐PD‐L1 pathway

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