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.

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 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 Curcumin Inhibits Joint Contracture through PTEN Demethylation and Targeting PI3K/Akt/mTOR Pathway in Myofibroblasts from Human Joint Capsule

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Ze Zhuang ◽  
Dongjie Yu ◽  
Zheng Chen ◽  
Dezhao Liu ◽  
Guohui Yuan ◽  
...  
Keyword(s):  
Mammalian Target Of Rapamycin ◽  
Clinical Problem ◽  
Joint Contracture ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Joint Injury ◽  
Specific Pcr ◽  
And Migration

Joint contracture is increasingly regarded as a clinical problem that leads to irreversible dysfunction of the joint. It is a pathophysiological process following joint injury, which is marked by the activation of myofibroblasts. There is currently no effective treatment for the prevention of joint contracture. Curcumin is a polyphenol pigment extracted from turmeric, which possesses anti-inflammatory, antioxidative, and antitumor properties. In the present study, we demonstrated that curcumin exerts a protective effect against joint contracture via the inhibition of myofibroblast proliferation and migration in a time- and concentration-dependent manner. Moreover, we indicated that phosphatase and tension homolog (PTEN) was downregulated in myofibroblasts in vitro and in the contracture capsule tissues of patients in vivo. Additionally, western blot analysis revealed a negative correlation between the expression levels of PTEN and the fibrosis marker protein alpha smooth muscle cell actin. Methylation-specific PCR results suggested that curcumin was able to demethylate PTEN in a similar manner to the demethylation agent 5-azacytidine, increasing PTEN expression and further inhibiting phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling. In conclusion, our data illustrate part of the mechanism of curcumin inhibition in joint contracture. These results support the hypothesis that curcumin may potentially be used as a novel candidate for the treatment of joint contracture.

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.

scholarly journals A Novel Substance P-Based Hydrogel for Increased Wound Healing Efficiency

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2215 ◽  
Author(s):  
Da Kim ◽  
Ji Jang ◽  
Song Jang ◽  
Jungsun Lee
Keyword(s):  
Wound Healing ◽  
Substance P ◽  
Dermal Fibroblasts ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes ◽  
In Vivo Experiments ◽  
And Migration ◽  
Proliferation And Migration

The neuropeptide substance P (SP) is known to stimulate wound healing by regulating the production of relevant cytokines as well as cell proliferation and migration. However, the therapeutic application of SP is limited by its low stability under biological conditions and oxidation during purification, formulation, and storage. To address this problem, we developed a novel formulation of SP as an SP gel, and investigated its wound healing activity both in vitro and in vivo. SP in SP gel was stable at various temperatures for up to 4 weeks. In vitro, SP gel exhibited more potential as a candidate wound-healing agent than SP alone, as evidenced by the observed increases in the proliferation and migration of human epidermal keratinocytes and human dermal fibroblasts. In vivo experiments showed that SP gel treatment enhanced the healing of full-thickness wounds in mice as compared to SP alone. These results demonstrate the benefits of SP gel as a promising topical agent for wound treatment.

scholarly journals Exosomes derived from human adipose mesenchymal stem cells attenuate hypertrophic scar fibrosis by miR-192-5p/IL-17RA/Smad axis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yan Li ◽  
Jian Zhang ◽  
Jihong Shi ◽  
Kaituo Liu ◽  
Xujie Wang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Hypertrophic Scar ◽  
Treated Group ◽  
Smad Pathway ◽  
In Vivo Experiments ◽  
Immunohistochemistry Staining ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background Hypertrophic scar (HS) is a fibro-proliferative disorder of dermis after burn or trauma and usually leads to esthetic disfiguration and functionary impairment for patients. Emerging evidences demonstrated ADSC-Exo could alleviate the visceral fibrosis, but little attention had been paid to its role in skin fibrosis. In the study, we would explore the effect of ADSC-Exo on HS and investigated the exact mechanism underlying the properties. Methods ADSC-Exo were isolated, identified, and internalized by HS-derived fibroblasts (HSFs). The effect of ADSC-Exo on the proliferation and migration of HSFs were detected by flow cytometry and Ki67 immunofluorescence staining, or scratch and trans-wells assays, respectively. RT-PCR, immunoblotting, immunofluorescence, and immunohistochemistry staining were used to evaluate the expression of IL-17RA, Col1, Col3, α-SMA, SIP1, and p-Smad2/p-Smad3 in HSFs stimulated with ADSC-Exo, miR-192-5p mimics, or inhibitors, IL-17RA siRNA and their negative controls. Digital morphology, H&E, Masson’s trichrome staining, and immunohistochemistry staining were performed to measure the effect of ADSC-Exo and Lv-IL-17RA shRNA on excisional wound of BALB/c mice. Results The verified ADSC-Exo effectively inhibited the proliferation and migration of HSFs, decreased the expression of Col1, Col3, α-SMA, IL-17RA, and p-Smad2/p-Smad3 and increased the levels of SIP1 in HSFs. Besides, the mice in ADSC-Exo-treated group demonstrated faster wound healing and less collagen deposition. Furthermore, miR-192-5p was highly expressed in ADSC-Exo and ADSC-Exosomal miR-192-5p ameliorated hypertrophic scar fibrosis. Meanwhile, miR-192-5p targeted the expression of IL-17RA to decrease the pro-fibrotic proteins levels. Moreover, IL-17RA was overexpressed in HS and HSFs, and knockdown IL-17RA alleviated the expression of Col1, Col3, α-SMA, and p-Smad2/p-Smad3 and increased the expression of SIP1 in HSFs. Most importantly, IL-17RA silence also facilitated wound healing, attenuated collagen production, and modulated Smad pathway in HSFs. Conclusions This study illustrated ADSC-Exo attenuated the deposition of collagen, the trans-differentiation of fibroblasts-to-myofibroblasts, and the formation of hypertrophic scar by in vitro and in vivo experiments. ADSC-Exosomal miR-192-5p targeted IL-17RA to regulate Smad pathway in hypertrophic scar fibrosis. ADSC-Exo could be a promising therapeutic strategy for clinical treatment of hypertrophic scar and the anti-fibrotic properties could be achieved by miR-192-5p/IL-17RA/Smad axis.

Alteration ofDACH1methylation patterns in lung cancer contributes to cell proliferation and migration

2018 ◽  
Vol 96 (5) ◽  
pp. 602-609 ◽  
Author(s):  
Yongjie Feng ◽  
Lin Wang ◽  
Mingyong Wang
Keyword(s):  
Lung Cancer ◽  
A549 Cells ◽  
Normal Lung ◽  
Migration And Invasion ◽  
And Migration ◽  
Methylation Patterns ◽  
Insight Into ◽  
Lower Expression ◽  
Proliferation And Migration

Lung cancer is the most common cause of cancer-related death. Non-small cell lung cancer (NSCLC) accounts for 80%–85% of total lung cancer cases. Dachshund homolog 1 (DACH1), is a protein encoded by the DACH1 gene in humans. DACH1 inhibits lung adenocarcinoma invasion and tumor growth but has a lower expression in NSCLC. To investigate the mechanisms of decreased DACH1 expression, its DNA methylation patterns were investigated. The results showed a higher methylation rate in NSCLC compared with the adjacent normal lung tissues. Cell transfection experiments showed that increased methylation impaired transcription factor transactivation. In vivo demethylation treatment and overexpression of DACH1 increased apoptosis and decreased migration and invasion in NSCLC A549 cells. Our research provides new insight into NSCLC pathogenesis and identifies a new therapeutic target.

scholarly journals Atom-Precise Fluorescent Copper Cluster for Tumor Microenvironment Targeting and Transient Chemodynamic Cancer Therapy

2021 ◽  
Author(s):  
Zhenzhen Yang ◽  
Anli Yang ◽  
Wang Ma ◽  
Kai Ma ◽  
Ya-Kun Lv ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Therapy ◽  
Dependent Manner ◽  
Metal Nanoclusters ◽  
Concentration Dependent Manner ◽  
In Vivo Experiments ◽  
Low Cytotoxicity ◽  
High Cytotoxicity

Abstract Background: Reactive oxygen species (ROS) have been widely studied for cancer therapy. Nevertheless, instability and aspecific damages to cellular biomolecules limited the application effect. Recently, significant research efforts have been witnessed in the flourishing area of metal nanoclusters (NCs) with atomically precise structures for targeted release of ROS but few achieved success towards targeting tumor microenvironment.Results: In this work, we reported an atomically precise nanocluster Cu6(C4H3N2S)6 (Cu6NC), which could slowly break and generate ROS once encountered with acidic. The as-prepared Cu6NC demonstrated high biological safety and efficient chemodynamic anti-tumor properties. Moreover, Cu6NC enabled transient release of ROS and contained targeting behavior led by the tumor microenvironment. Both in vitro and in vivo experiments confirmed that Cu6NC demonstrated a low cytotoxicity for normal cells, while presented high cytotoxicity for tumor cells with a concentration-dependent manner.Conclusions: This work not only reported a promising candidate for chemodynamic cancer therapy, but also paved the route to address clinical issues at the atomic level.

scholarly journals Visfatin Promotes Wound Healing Through the Activation of ERK1/2 and JNK1/2 Pathway

2018 ◽  
Author(s):  
Byungcheol Lee ◽  
Jisun Song ◽  
Arim Lee ◽  
Daeho Cho ◽  
Tae Sung Kim
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Human Keratinocytes ◽  
Dermal Fibroblasts ◽  
Dependent Manner ◽  
Vegf Expression ◽  
And Migration ◽  
Proliferation And Migration

Visfatin, a member of the adipokine family, plays an important role in many metabolic and stress responses. The mechanisms underlying the direct therapeutic effects of visfatin on wound healing have not been reported yet. In this study, we examined the effects of visfatin on wound healing in vitro and in vivo. Visfatin enhanced the proliferation and migration of human dermal fibroblasts (HDFs) and keratinocytes, and significantly increased the expression of wound healing-related vascular endothelial growth factor (VEGF) in vitro and in vivo. Treatment of HDFs with visfatin induced activation of both extracellular signal-regulated kinases 1 and 2 (ERK1/2) and c-Jun N-terminal kinases 1 and 2 (JNK1/2) in a time-dependent manner. Inhibition of ERK1/2 and JNK1/2 led to a significant decrease in visfatin-induced proliferation and migration of HDFs. Importantly, blocking VEGF with its neutralizing antibodies suppressed the visfatin-induced proliferation and migration of HDFs and human keratinocytes, indicating that visfatin induces the proliferation and migration of HDFs and human keratinocytes via increased VEGF expression. Moreover, visfatin effectively improved wound repair in vivo, which was comparable to the wound healing activity of epidermal growth factor (EGF). Taken together, we demonstrate that visfatin promotes the proliferation and migration of HDFs and human keratinocytes by inducing VEGF expression and can be used as a potential novel therapeutic agent for wound healing.

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