scholarly journals The expression, significance and function of cancer susceptibility candidate�9 in lung squamous cell carcinoma: A bioinformatics and in�vitro investigation

2019 ◽  
Author(s):  
Li Gao ◽  
Yi‑Nan Guo ◽  
Jiang‑Hui Zeng ◽  
Fu‑Chao Ma ◽  
Jie Luo ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cancer Susceptibility ◽  
Lung Squamous Cell Carcinoma ◽  
In Vitro Investigation ◽  
And Function

scholarly journals Hypoxia-mediated YTHDF2 overexpression promotes lung squamous cell carcinoma progression by activation of the mTOR/AKT axis

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Peng Xu ◽  
Kang Hu ◽  
Ping Zhang ◽  
Zhi-Gang Sun ◽  
Nan Zhang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Lung Squamous Cell Carcinoma ◽  
Akt Signaling ◽  
In Vitro Assays ◽  
Domain Family ◽  
Yth Domain

Abstract Background N6-methyladenosine (m6A) is a dynamic and reversible internal RNA structure of eukaryotic mRNA. YTH domain family 2 (YTHDF2), an m6A-specific reader YTH domain family, plays fundamental roles in several types of cancer. However, the function of YTHDF2 in lung squamous cell carcinoma (LUSC) remains elusive. Methods The knockdown and overexpression of YTHDF2 in LUSC cells were conducted to detect the biological characteristics of YTHDF2. In vivo assays, the role of YTHDF2 in tumor growth was further uncovered. In vitro assays, YTHDF2 was confirmed to be involved in activating the mTOR/AKT signaling and YTHDF2 overexpression induced the EMT process in LUSC. Clinically, immunohistochemical staining revealed the relationship between YTHDF2 expression levels and the clinicopathological characteristics of lung squamous cell carcinoma patients. Moreover, quantitative PCR (qPCR), western blot, CCK8 assay, transwell assay, and wound-healing assay were used to detect the expression level and function of YTHDF2 under hypoxia exposure in LUSC cells. Results The results showed that hypoxia-mediated YTHDF2 overexpression promotes cell proliferation and invasion by activating the mTOR/AKT axis, and YTHDF2 overexpression induces the EMT process in LUSC. Moreover, YTHDF2 is closely associated with pN (pN– 37.0%, pN + 73.9%; P = 0.002) and pTNM stage (pI 50.0%, PII 43.3%, pIIIa 80.6%; P = 0.007), ultimately resulting in poor survival for LUSC patients. Conclusion In brief, the results highlight high-YTHDF2 expression predicted a worse prognosis of LUSC, while hypoxia-mediated YTHDF2 overexpression promotes lung squamous cell carcinoma progression by activation of the mTOR/AKT signaling pathway.

scholarly journals Vasohibin 2 Promotes Lymphangiogenesis of Lung Squamous Cell Carcinoma Through Snail-dependent VEGF-D Signaling Pathway

2020 ◽  
Author(s):  
Pengpeng Liu ◽  
Rui Zhang ◽  
Lei Han ◽  
Xiao Zhang ◽  
Yingnan Ye ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Endothelial Cells ◽  
Tumor Growth ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Lymphatic Metastasis ◽  
Poor Prognosis ◽  
Lung Squamous Cell Carcinoma ◽  
Secondary Site

Abstract Backgroumd: Tumor metastasis is a process in which tumor cells enter the lymphatic vessels and blood vessels and then spread to the secondary site where they form secondary tumors. In vascular biology, angiogenesis and anti-angiogenesis therapy have been extensively studied, however, the molecular mechanisms involved in lymphangiogenesis and lymphatic metastasis remain unclear.Methods: We analyzed mRNA expression profiles of 937 primary lung squamous cell carcinoma (LUSC) samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to screen the most differentially expressed genes related to the poor prognosis of LUSC patients and validated in an independent Chinese LUSC cohort. We focused on Vasohibin 2 (VASH2) and investigated its biological functions in LUSC proliferation, apoptosis, migration, invasion, as well as lymphangiogenesis by forced over-expressing VASH2 in LUSC cell line H520 in vitro. We also investigated the anti-tumor efficacy of VASH2 target treatment in LUSC xenograft-bearing mice models.Results: We identified 12 genes closely related to poor prognosis of LUSC patients, among which VASH2 was validated in an independent Chinese LUSC cohort and displayed high potential of lymphatic metastasis. VASH2 promoted the proliferation and invasion of LUSC cells both in vitro and vivo. Forced over-expression of VASH2 in LUSC cells promoted the amplification and tube-formation of human umbilical vein endothelial cells (HUVECs) and human lymphatic endothelial cells (HLECs) cells via up-regulating vascular endothelial growth factor-D (VEGF-D) production which could be reversed by Snail inhibition. Furthermore, blocking VASH2/VEGF-D signaling using specific antibodies dramatically inhibited tumor growth in mice by interfering proliferation of cancer cells and lymphangiogenesis in tumor tissues. Conclusion: In conclusion, VASH2 facilitated lymphangiogenesis and tumor growth in a Snail-dependent manner which might serve as a novel biomarker for early diagnosis and prognosis prediction, as well as a potential therapeutic target in LUSC.Statement of conflict of interest: The authors declare no potential conflicts of interest.

scholarly journals FGFR1 Promotes Tumor Immune Evasion via YAP-Mediated PD-L1 Expression Upregulation in Lung Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Min Lu ◽  
Kaixuan Wang ◽  
Wenxiang Ji ◽  
Yongfeng Yu ◽  
Ziming Li ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
T Cells ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Immune Evasion ◽  
Lung Squamous Cell Carcinoma ◽  
Tumor Immune Evasion ◽  
Programmed Death

Abstract Background: Variations in fibroblast growth factor receptor 1 (FGFR1), which occur frequently, are common driver mutations of lung squamous cell carcinoma. Immune checkpoint inhibitors targeting programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) are powerful anticancer weapons. Activation of FGFR1 leads to tumorigenesis through multiple downstream molecules, including Yes-associated protein (YAP), but whether and how FGFR1 regulates tumor immune evasion remain largely unclear. Methods: H520 and HCC95 cells were treated with siRNA and plasmids to increase or decrease the expression of FGFR1, YAP and PD-L1, as assessed by molecular assays of protein and mRNA expression. The interaction between YAP and PD-L1 was verified by chromatin immunoprecipitation. After FGFR1 knockdown by shRNA, cancer cells were cocultured with Jurkat T cells, and then cell proliferation and activity were assessed. In C57BL/6 mice, the tumor immune microenvironment was analyzed by flow cytometry, immunofluorescence and immunohistochemistry after FGFR1 knockdown. The effect of the combination of FGFR1 knockdown and PD-1 blockade was explored both in vitro and in vivo. Results: In H520 and HCC95 cells, FGFR1 upregulated PD-L1 expression via YAP, and YAP initiated the transcription of PD-L1 after binding to its promoter region. Both in vitro and in vivo, FGFR1 knockdown decreased tumor growth and reduced immune escape and reactivation of T cells. The combination of FGFR1 knockdown and PD-1 blockade synergistically exerted antitumor effects. In human LSQCC, the expression of fibroblast growth factor 2 (FGF2), the activator of FGFR1, was positively correlated with that of PD-L1 at the mRNA level. Conclusions: The FGFR1/YAP/PD-L1 regulatory axis mediates tumor-associated immune suppression in lung squamous cell carcinoma, and FGFR1 knockdown reactivates T cells in the tumor microenvironment. Synergistic inhibition of both FGFR1 and PD-1/PD-L1 may be a possible treatment for lung cancer patients.

MIR205HG facilitates carcinogenesis of lung squamous cell carcinoma in vitro revealed by long noncoding RNA profiling

2020 ◽  
Vol 52 (4) ◽  
pp. 371-381 ◽  
Author(s):  
Yan Chang ◽  
Xinying Xue ◽  
Chunsun Li ◽  
Wei Zhao ◽  
Yongfu Ma ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Noncoding Rna ◽  
Lung Squamous Cell Carcinoma ◽  
Clinical Samples ◽  
Lung Cancers ◽  
Rna Profiling ◽  
Whole Transcriptome Sequencing

Abstract As a subtype of non-small-cell lung cancer, lung squamous cell carcinoma (LUSC) accounts for one-fifth of all lung cancers. Unfortunately, no specific targetable aberration has yet been identified. Hence, it is of huge urgency and potential to identify aberrantly regulated genes in LUSC. Here, five pairs of LUSC samples and their corresponding adjacent tissues were subject to whole transcriptome sequencing. Our results showed that CTD-2562J17.6 and FENDRR were significantly downregulated while MIR205HG, LNC_000378, RP11-116G8.5, RP3-523K23.2, and RP5-968D22.1 were significantly upregulated in all five LUSC samples. Importantly, MIR205HG was upregulated in LUSC clinical samples as well as in LUSC cell lines. Interestingly, our results demonstrated that the expression level of MIR205HG is positively correlated with the malignancy. In addition, MIR205HG is required for LUSC cell growth and cell migration. Most importantly, our results showed that MIR205HG prohibits LUSC apoptosis via regulating Bcl-2 and Bax. Taken together, our data shed lights on the lncRNA regulatory nexus that controls the carcinogenesis of LUSC and provided potential novel diagnostic markers and therapeutic targets for LUSC.

Evaluation of the in vitro Chemosensitivity and Correlation with Clinical Outcomes in Lung Cancer using the ATP-TCA

2018 ◽  
Vol 18 (1) ◽  
pp. 139-145 ◽  
Author(s):  
Zhiyao Chen ◽  
Shichao Zhang ◽  
Sheng Ma ◽  
Chang Li ◽  
Chun Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Clinical Outcomes ◽  
Squamous Cell ◽  
Lung Squamous Cell Carcinoma ◽  
Lung Cancer Patients ◽  
In Vitro Chemosensitivity

Background and Objective: Multiple drug resistance (MDR) to chemotherapeutic agents often leads to a failure to respond to chemotherapy. We utilized an in vitro chemosensitivity test to identify sensitive and effective chemotherapeutic drugs and further elucidated the correlation between the in vivo chemosensitivity and clinical outcomes. Methods: Here, we evaluated the in vitro chemosensitivity and MDR of 120 lung cancer patients to eight singledrug chemotherapies and of 291 lung cancer patients to seven chemotherapy regimens using an ATP-based tumor chemosensitivity assay (ATP-TCA). Additionally, the chemosensitivity profiles of lung adenocarcinoma patients (284 cases) and lung squamous cell carcinoma patients (90 cases) to these single-drug and chemotherapy regimens were compared. Furthermore, the correlations between the chemosensitivity and clinical outcomes were investigated in 16 stage III squamous cell carcinoma patients. Results and Conclusion: PTX (51.7%), TXT (43.3%), GEM (12.5%), PTX+DDP (62.5%), TXT+L-OHP (54.3%) and VP-16+DDP (16.2%) had the highest in vitro chemosensitivity rates. Approximately 31.7% of patients developed resistance to all eight single-drug chemotherapies, and 25.8% of patients displayed resistance to all seven chemotherapy regimens. In addition, lung squamous cell carcinoma was significantly more sensitive to GEM and MTA+DDP than lung adenocarcinoma (P<0.05). Further analysis showed that patients with higher drug sensitivity tended to have longer disease-free survival (18 months vs. 8.5 months) than patients displaying drug resistance (P<0.05). These results suggest that the implementation of in vitro drug susceptibility testing before chemotherapy can effectively prevent the occurrence of primary drug resistance and inappropriate drug treatment.

The anti-tumor effect of regorafenib in lung squamous cell carcinoma in vitro

2018 ◽  
Vol 503 (2) ◽  
pp. 1123-1129 ◽  
Author(s):  
Xiu Hu ◽  
Lin-wen Wu ◽  
Zuo-yan Zhang ◽  
Meng-ling Chen ◽  
Yang-ling Li ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Lung Squamous Cell Carcinoma
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