scholarly journals Interferon Regulatory Factor 9 Promotes Lung Cancer Progression via Regulation of Versican

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 208
Author(s):  
David Brunn ◽  
Kati Turkowski ◽  
Stefan Günther ◽  
Andreas Weigert ◽  
Thomas Muley ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
Lung Tumor ◽  
Interferon Regulatory Factor ◽  
Human Lung Cancer ◽  
Regulatory Factor ◽  
And Migration ◽  
Proliferation And Migration

Transcription factors can serve as links between tumor microenvironment signaling and oncogenesis. Interferon regulatory factor 9 (IRF9) is recruited and expressed upon interferon stimulation and is dependent on cofactors that exert in tumor-suppressing or oncogenic functions via the JAK-STAT pathway. IRF9 is frequently overexpressed in human lung cancer and is associated with decreased patient survival; however, the underlying mechanisms remain to be elucidated. Here, we used stably transduced lung adenocarcinoma cell lines (A549 and A427) to overexpress or knockdown IRF9. Overexpression led to increased oncogenic behavior in vitro, including enhanced proliferation and migration, whereas knockdown reduced these effects. These findings were confirmed in vivo using lung tumor xenografts in nude mice, and effects on both tumor growth and tumor mass were observed. Using RNA sequencing, we identified versican (VCAN) as a novel downstream target of IRF9. Indeed, IRF9 and VCAN expression levels were found to be correlated. We showed for the first time that IRF9 binds at a newly identified response element in the promoter region of VCAN to regulate its transcription. Using an siRNA approach, VCAN was found to enable the oncogenic properties (proliferation and migration) of IRF9 transduced cells, perhaps with CDKN1A involvement. The targeted inhibition of IRF9 in lung cancer could therefore be used as a new treatment option without multimodal interference in microenvironment JAK-STAT signaling.

Proliferation and Migration of Lung Cancer Could be Inhibited by Oxymatrine through the Regulation for miR-520/VEGF

2019 ◽  
Vol 47 (04) ◽  
pp. 865-878 ◽  
Author(s):  
Wen Zhou ◽  
Yunshan Wu ◽  
Miao Pan ◽  
Daojun Liu ◽  
Bo Liu
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
Direct Interaction ◽  
Significant Negative Correlation ◽  
Cancer Proliferation ◽  
In Vivo Experiments ◽  
And Migration ◽  
Proliferation And Migration

Recent evidence suggests that Oxymatrine (OMT) has excellent effects in anticancer. The mechanism, however, remains unclear. In the present study, we investigated the potential mechanism of OMT against cancer. The differential expression of miRNA was screened by miRNA array. The expression of miRNA-520 and VEGF in lung cancer was assayed by real-time PCR, Western blot and immunohistochemistry, respectively. The direct interaction between miRNA-520 and VEGF was assayed by luciferase activity assay and their roles in lung cancer proliferation, invasion and migration were analyzed in vivo and in vitro. We found that miR-520 was markedly down-regulated and VEGF was markedly up-regulated in lung cancer tissues compared with adjacent normal tissues, which had significant negative correlation. Dual-luciferase assays confirmed that miR-520 directly targeting VEGF by binding to its upstream promoter region. Through in vitro and in vivo experiments, we found that different doses of OMT could up-regulate miR-520, selectively inhibit VEGF and thus inhibit the proliferation and migration of lung cancer. Our findings indicate that OMT inhibited cancer progression and metastasis by upregulation of miR-520 and downregulation of VEGF, which provide new support for OMT may be as a novel anticancer drug for the treatment of lung cancer in the future.

scholarly journals POU2F2 promotes the proliferation and motility of lung cancer cells by activating AGO1

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ronggang Luo ◽  
Yi Zhuo ◽  
Quan Du ◽  
Rendong Xiao
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Human Lung ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Cancer Tissues

Abstract Background To detect and investigate the expression of POU domain class 2 transcription factor 2 (POU2F2) in human lung cancer tissues, its role in lung cancer progression, and the potential mechanisms. Methods Immunohistochemical (IHC) assays were conducted to assess the expression of POU2F2 in human lung cancer tissues. Immunoblot assays were performed to assess the expression levels of POU2F2 in human lung cancer tissues and cell lines. CCK-8, colony formation, and transwell-migration/invasion assays were conducted to detect the effects of POU2F2 and AGO1 on the proliferaion and motility of A549 and H1299 cells in vitro. CHIP and luciferase assays were performed for the mechanism study. A tumor xenotransplantation model was used to detect the effects of POU2F2 on tumor growth in vivo. Results We found POU2F2 was highly expressed in human lung cancer tissues and cell lines, and associated with the lung cancer patients’ prognosis and clinical features. POU2F2 promoted the proliferation, and motility of lung cancer cells via targeting AGO1 in vitro. Additionally, POU2F2 promoted tumor growth of lung cancer cells via AGO1 in vivo. Conclusion We found POU2F2 was highly expressed in lung cancer cells and confirmed the involvement of POU2F2 in lung cancer progression, and thought POU2F2 could act as a potential therapeutic target for lung cancer.

scholarly journals Knockdown of LncRNA LINC00958 Inhibits the Proliferation and Migration of NSCLC Cells by MiR-204-3p/KIF2A Axis

2021 ◽  
Vol 30 ◽  
pp. 096368972110255
Author(s):  
Qing Wang ◽  
Kai Li ◽  
Xiaoliang Li
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Tumor Model ◽  
Luciferase Reporter ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Increasing evidence suggests that long non-coding RNAs (lncRNAs) function in the tumorigenesis of NSCLC. LINC00958, a newly identified lncRNA, has been reported to be closely linked to tumorigenesis in several cancers. However, its specific role in NSCLC remains unclear. In this study, we determined the expression of LINC00958 in NSCLC by RT-qPCR analysis and evaluated cell proliferation and migration by CCK-8 and transwell assays, respectively. We established a xenograft tumor model to examine the effect of LINC00958 on tumor growth in vivo. Luciferase reporter assays were performed to determine the interaction between LINC00958 and miR-204-3p and the interaction between miR-204-3p and KIF2A. We found that LINC00958 was up-regulated in NSCLC tissues and cell lines. Down-regulation of LINC00958 inhibited cell proliferation and migration in vitro and suppressed tumor growth in vivo. Besides, miR-204-3p was identified as a target of LINC00958 and miR-204-3p inhibitor could reverse the inhibitory effect of LINC00958 knockdown on proliferation and migration of NSCLC cells. We also validated that KIF2A, a direct target of miR-204-3p, was responsible for the biological role of LINC00958. KIF2A antagonized the effect of miR-204-3p on NSCLC cell proliferation and migration and was regulated by LINC00958/miR-204-3p. Taken together, these data indicate that the LINC00958/miR-204-3p/KIF2A axis is critical for NSCLC progression, which might provide a potential therapeutic target of NSCLC.

scholarly journals TMEM16A, a Homoharringtonine Receptor, as a Potential Endogenic Target for Lung Cancer Treatment

2021 ◽  
Vol 22 (20) ◽  
pp. 10930
Author(s):  
Shuai Guo ◽  
Xue Bai ◽  
Sai Shi ◽  
Yawen Deng ◽  
Xianjiang Kang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Normal Lung ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
In Vivo Experiments ◽  
Incidence And Mortality ◽  
And Migration ◽  
Proliferation And Migration

Lung cancer has the highest rate of incidence and mortality among all cancers. Most chemotherapeutic drugs used to treat lung cancer cause serious side effects and are susceptible to drug resistance. Therefore, exploring novel therapeutic targets for lung cancer is important. In this study, we evaluated the potential of TMEM16A as a drug target for lung cancer. Homoharringtonine (HHT) was identified as a novel natural product inhibitor of TMEM16A. Patch-clamp experiments showed that HHT inhibited TMEM16A activity in a concentration-dependent manner. HHT significantly inhibited the proliferation and migration of lung cancer cells with high TMEM16A expression but did not affect the growth of normal lung cells in the absence of TMEM16A expression. In vivo experiments showed that HHT inhibited the growth of lung tumors in mice and did not reduce their body weight. Finally, the molecular mechanism through which HHT inhibits lung cancer was explored by western blotting. The findings showed that HHT has the potential to regulate TMEM16A activity both in vitro and in vivo and could be a new lead compound for the development of anti-lung-cancer drugs.

scholarly journals Ral GTPases targeted by miR-215-5p promote lung cancer proliferation and migration

2020 ◽  
Author(s):  
Hao Zhu ◽  
Shufang Cui ◽  
Gentao Fan ◽  
Jing Zhang ◽  
Xiaofeng Hua ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Western Blot ◽  
Luciferase Assay ◽  
Rt Pcr ◽  
Cancer Proliferation ◽  
Ral Gtpases ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background The Ras-like guanosine triphosphatases (Ral GTPases) belongs to the Ras superfamily of small GTPases. Ras mutations occur in more than one in three human tumors. However, treatments acting directly on Ras post-translational modifications were developed and have been manufactured for many years, although they have demonstrated poor clinical performance. Ral GTPases include RalA and RalB, seem to be a new potential pathway downstream of mutant Ras. Methods In this study, we examined protein and mRNA level of Ral GTPases in lung specimens from 12 lung cancer patients using Western Blot and RT-PCR. The effects of RalA and RalB on the proliferation and migration were examined by functional tests in vitro and in vivo. The binding site in miR-215-5p and RalA or RalB was predicted using bioinformatics software and proved by Western Blot, RT-PCR and luciferase assay. The effect of miR-215-5p on RalA and RalB were examined in cell lines and xenograft mice. Results Here, we reported that miR-215-5p was downregulated in human lung cancer tissues compared with noncancerous tissues, whereas the expression level of Ral GTPases was higher. We further verified that the negative regulation of Ral GTPases by miR-215-5p could inhibit the proliferation and migration of lung cancer in vitro and in vivo. Conclusion In this study, we reported that RalA and RalB promote lung cancer proliferation and migration. Moreover, we identified miR-215-5p as a tumor suppressor that targets Ral GTPases. Our results may offer therapeutic opportunities in lung cancer.

scholarly journals High glucose contributes to the proliferation and migration of non-small-cell lung cancer cells via GAS5-TRIB3 axis

2018 ◽  
Vol 38 (2) ◽  
Author(s):  
Cheng-Zhi Ding ◽  
Xu-Feng Guo ◽  
Guo-Lei Wang ◽  
Hong-Tao Wang ◽  
Guang-Hui Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Progression ◽  
Cell Lung Cancer ◽  
High Glucose ◽  
Small Cell ◽  
Small Cell Lung ◽  
And Migration ◽  
Proliferation And Migration

Despite the growing number of studies exhibiting an association of diabetes mellitus (DM) and lung cancer progression, the concrete mechanism of DM aggravating lung cancer has not been elucidated. The present study was to investigate whether and how high glucose (HG) contributes to the proliferation and migration of non-small-cell lung cancer (NSCLC) cells in vitro. In the present study, we confirmed that HG promoted the proliferation and migration of NSCLC cells, and also induced an anti-apoptotic effect on NSCLC cells. Moreover, HG inhibited the expression of growth arrest-specific 5 (GAS5) in NSCLC cells but elevated the protein level of tribbles homolog 3 (TRIB3). GAS5 overexpression promoted the degradation of TRIB3 protein by ubiquitination and inhibited the HG-induced proliferation, anti-apoptosis, and migration of NSCLC cells. Importantly, TRIB3 overexpression reversed the effects of GAS5 on the HG-treated NSCLC cells. Taken together, down-regulated GAS5 by HG significantly enhanced the proliferation, anti-apoptosis, and migration in NSCLC cells through TRIB3, thus promoting the carcinogenesis of NSCLC.

Sign in / Sign up

Export Citation Format

Share Document