CIAPIN1 is a potential target for apoptosis of multiple myeloma

2019 ◽  
Vol 9 (9) ◽  
pp. 1106-1111
Author(s):  
Xiao-Bo Wang ◽  
Le-Ping Yan ◽  
Li-Hua Yuan ◽  
Bo Lu ◽  
Dong-Jun Lin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Colony Formation ◽  
Bone Marrow Cells ◽  
Xenograft Model ◽  
Soft Agar ◽  
Normal Human ◽  
Related Proteins

This study firstly aimed to reveal the gene expression differences of CIAPIN1 between myelomas cells from bone marrow cells of multiple myeloma patients and normal human, and subsequently investigate the regulation role of this gene on tumorigenicity ability of multiple myeloma (MM) cell line U266 via in vitro colony formation and in vivo xenograft studies. RT-PCR results obtained from 18 MM patients and 10 health people showed that the expression of CIAPIN1 gene was 4 times higher in normal human compared to MM patients. Besides, CIAPIN1 siRNA (si-CIAPIN1) transfected U266 cells presented higher proliferation ratio and superior colony forming ability than U266 cells and U266 cells transfected with non-coding siRNA (controls) evaluated by CCK8 test and soft agar colony formation assay, respectively. In a mice MM xenograft model, the si-CIAPIN1 transfected U266 cells induced the biggest tumor compared to the controls. Furthermore, CIAPIN1 overexpressed U266 cells were developed and compared with the si-CIAPIN1 transfected U266 cells to study the role of CIAPIN1 in the production of apoptosis related proteins in U266 cells. Results indicated that CIAPIN1 facilitated apoptosis promoting proteins expression in U266 cells, such as upregulation of BAX, BAK, Bcl-xs and BIM, and downregulation of p38, PKC, Bcl-2 and Bcl-xl proteins. Therefore, CIAPIN1 can be a potential suppression target gene in multiple myeloma.

scholarly journals Shengma Biejia Decoction Inhibits Cell Growth in Multiple Myeloma by Inducing Autophagy-Mediated Apoptosis Through the ERK/mTOR Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Huibo Dai ◽  
Bangyun Ma ◽  
Xingbin Dai ◽  
Jie Pang ◽  
Jingyu Wang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Caspase 3 ◽  
Malignant Tumors ◽  
Xenograft Model ◽  
Annexin V ◽  
Mtor Pathway ◽  
Therapy Strategy ◽  
Related Proteins

Shengma Biejia decoction (SMBJD), a traditional Chinese formula recorded in the Golden Chamber, has been widely used for the treatment of malignant tumors. However, its underlying molecular targets and mechanisms are still unclear. This study showed that SMBJD inhibited tumor growth and stimulated hemogram recovery significantly in a multiple myeloma xenograft model. Western blot and immunohistochemistry assays of tumor tissues showed that SMBJD reduced the ratio of autophagy-related proteins LC3-II/LC3-I, while P62 and apoptosis-related proteins cleaved caspase-3/caspase-3 and Bax/Bcl-2 were upregulated. In vitro experiments demonstrated the time-dependent and dose-dependent cytotoxicity of SMBJD on multiple myeloma cell lines H929 and U266 through MTT assays. The LC3-II/LC3-I ratio and number of GFP-LC3 puncta showed that SMBJD inhibited the autophagy process of H929 and U266 cells. Moreover, both SMBJD and 3-methyladenine (3-MA) caused a decrease in LC3-II/LC3-I, and SMBJD could not reverse the upregulation of LC3-II/LC3-I caused by bafilomycin A1 (Baf-A1). Furthermore, the results of annexin V-FITC and propidium iodide double staining demonstrated that SMBJD treatment induced the apoptosis of H929 and U266 cells. These data prove that SMBJD inhibits autophagy and promotes apoptosis in H929 and U266 cells. The results also show that rapamycin could reduce the rate of SMBJD-induced apoptosis in H929 and U266 cells, at a concentration which had no effect on apoptosis but activated autophagy. In addition, analysis of the mechanism indicated that levels of phosphorylated ERK and phosphorylated mTOR were increased by treatment with SMBJD in vivo and in vitro. These results indicate that SMBJD, an old and effective herbal compound, could inhibit the viability of H929 and U266 cells and induce autophagy-mediated apoptosis through the ERK/mTOR pathway. Thus, it represents a potential therapy strategy for multiple myeloma.

scholarly journals Recombinant gibbon interleukin-3 acts synergistically with recombinant human G-CSF and GM-CSF in vitro

Blood ◽  
1988 ◽  
Vol 71 (6) ◽  
pp. 1596-1600 ◽  
Author(s):  
RL Paquette ◽  
JY Zhou ◽  
YC Yang ◽  
SC Clark ◽  
HP Koeffler
Keyword(s):  
Colony Formation ◽  
Clinical Utility ◽  
Bone Marrow Cells ◽  
Soft Agar ◽  
Interleukin 3 ◽  
Gm Csf ◽  
Normal Human ◽  
Stimulating Factor ◽  
Normal Human Bone Marrow

Recombinant gibbon interleukin-3 (IL-3) is a multilineage hematopoietic colony-stimulating factor (CSF) that recently was cloned and found to be highly homologous with human IL-3. Gibbon IL-3, as well as human granulocyte-CSF (G-CSF) and human granulocyte-macrophage CSF (GM-CSF), stimulated normal human bone marrow cells to form myeloid colonies in soft agar in a sigmoidal dose-response manner. When IL-3 was added to increasing concentrations of G-CSF or GM-CSF, synergistic colony formation occurred as compared with the effects of each CSF alone. Synergism was also noted when G-CSF was added with GM-CSF and when all the CSFs were added simultaneously. The combination of IL-3 and GM-CSF was less stimulatory than all the other CSF combinations. At day 11 of culture, IL-3 induced granulocyte-macrophage (38%), eosinophil (30%), granulocyte (18%), and macrophage (14%) colony formation. In summary, gibbon IL-3 is a growth factor that can synergize with other CSFs to enhance proliferation of myeloid-committed progenitors, suggesting that combinations of CSFs may have clinical utility in patients with neutropenia of various etiologies.

scholarly journals Glaucocalyxin A suppresses multiple myeloma progression in vitro and in vivo through inhibiting the activation of STAT3 signaling pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mei Li ◽  
Cailong Chen ◽  
Qian Wang ◽  
Xiaolu Jiang ◽  
Lanlan Tan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Multiple Myeloma ◽  
Cell Proliferation ◽  
Xenograft Model ◽  
Mice Model ◽  
Cycle Arrest ◽  
Nude Mice Model

Abstract Background Multiple myeloma (MM) is the most common malignant hematological disease in the people worldwide. Glaucocalyxin A (GLA) is a bioactive ent-kauranoid diterpenoid, that is derived from Rabdosia japonica var. GLA has been demonstrated that it had various pharmacological activities, such as anti-coagulation, anti-bacterial, anti-tumor, anti-inflammation, antioxidant activities. Although GLA has effective anti-tumor properties, its effects on multiple myeloma remain unclear. The aim of this study was to examine the possible anti-cancer effects of GLA and their molecular mechanisms on MM cells in vitro and in vivo. Methods To evaluate the role of GLA on the proliferation of MM cells in vitro and in vivo, we used MTT method to detect the role of GLA on the proliferation of MM cells. Cell apoptosis and cell cycle assay were evaluated by flow cytometry. Protein expressions in GLA-treated and untreated MM cells were evaluated by western blot analyses. MM xenograft nude mice model was used to investigate the role of GLA on the proliferation of MM cells in vivo. IHC assay was used to examine the role of GLA on the MM xenograft model in vivo. Results In the present study, we firstly reported the potent anti-myeloma activity of GLA on MM cells. We found that GLA could induce apoptosis in vitro and in vivo. GLA could inhibit the phosphorylation of the signal transducer and activator of transcription 3 (STAT3) and downregulate interleukin IL-6 induced STAT3 phosphorylation in MM. Overexpression of STAT3 could significantly prevent apoptosis induced by GLA; while knockdown of STAT3 enhanced it. Moreover, GLA could inhibit cell proliferation by inducing the cell cycle arrest. GLA reduced the expression of cell cycle-related proteins CCNB1, CCND1, CCND2, and CCND3 and increased the expression of p21 in MM cell lines. In addition, in the MM xenograft nude mice model, GLA exhibited very good anti-myeloma activity. Administration of GLA almost completely inhibited tumor growth within 19 days without physical toxicity. And the IHC results showed GLA significantly inhibited cell proliferation and interfered STAT3 pathway on MM xenograft model tumor tissues. Conclusions Taken together, our present research indicated that GLA inhibits the MM cell proliferation, induces MM cell apoptosis and cell cycle arrest through blocking the activation of STAT3 pathway. Thus, GLA may be a potential therapeutic candidate for MM patients in the future.

scholarly journals LDH-A promotes malignant behavior via activation of epithelial-to-mesenchymal transition in lung adenocarcinoma

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Xiao-ming Hou ◽  
Shu-qiao Yuan ◽  
Da Zhao ◽  
Xiao-jun Liu ◽  
Xin-an Wu
Keyword(s):  
Tumor Growth ◽  
Lung Adenocarcinoma ◽  
Cancer Cells ◽  
Colony Formation ◽  
Epithelial Mesenchymal Transition ◽  
Xenograft Model ◽  
Mesenchymal Transition

Abstract Lactate dehydrogenase A (LDH-A) is a key enzyme during glycolysis, which increases the synthesis of related proteins and has elevated activity in cancer cells. The role of LDH-A in lung adenocarcinoma (LUAD) progression was investigated in the present study. Expression levels of LDH-A were assessed in LUAD samples, and the relationship between LDH-A expression status and the prognosis of LUAD patients was confirmed. The effect of LDH-A on proliferation, invasion, migration, and colony formation of cancer cells was assessed. We further determined the role of LDH-A in tumor growth in vivo by using xenograft LUAD tumor models. The potential mechanism of LDH-A promotion in LUAD progression was explored. LDH-A showed an abnormally high expression in LUAD, which is closely associated with poor prognosis in patients with LUAD. In in vitro experiments, silencing LDH-A expression in LUAD cells could effectively inhibit proliferation, invasion, migration, and colony formation of cancer cells. In in vivo experiments, tumor growth was markedly inhibited by LDH-A silencing in a xenograft model of LUAD. Notably, LDH-A could also promote tumor progression by regulating epithelial–mesenchymal transition (EMT)-related molecules. LDH-A can promote the malignant biological behaviors of LUAD cells, and thus can be a potential target for LUAD treatment.

scholarly journals Lycorine Downregulates HMGB1 to Inhibit Autophagy and Enhances Bortezomib Activity in Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3265-3265
Author(s):  
Mridul Roy ◽  
Long Liang ◽  
Xiaojuan Xiao ◽  
Yuanliang Peng ◽  
Yuhao Luo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Conflicts Of Interest ◽  
Single Agent ◽  
Xenograft Model ◽  
Hmgb1 Expression ◽  
Resistant Cells

Abstract Multiple myeloma (MM) is the second most prevalent hematologic malignancy, characterized by the infiltration of malignant plasma cells into bone marrow. In spite of current efficient therapeutic regimens, which have significantly increased patients overall survival, the major features inevitably present in MM are the intrinsic and acquired resistance with nearly universal relapse. In addition, the diverse heterogeneous characteristics of this largely incurable disease emphasize the importance of innovative therapies and identification of more effective drugs. Autophagy removes defective cellular organelles, protein aggregates, and intracellular microbes and is associated with cell survival and tumor maintenance. Inhibition of autophagy enhances sensitivity of a number of anticancer agents and induces cell death in MM. High-mobility group box-1 (HMGB1) protein plays an important subcellular localization-dependent role during autophagy. The importance of HMGB1 for induction of autophagy and tumor development has made this protein as a novel target for cancer therapy. Lycorine is a natural alkaloid with significant anti-cancer activity. While previous studies mainly showed lycorine as a potential apoptosis inducer, recent studies stated that apoptosis is not the primary underlying anti-proliferative mechanism of this compound. This led the interest to investigate the role of lycorine on other cell maintenance systems, such as autophagy. In addition single-agent efficacy of lycorine or in combination with other anti-MM agents has not been evaluated in vivo. Herein we investigated the anti-MM effect of lycorine and the role of this natural agent on regulation of autophagy in vitro and in vivo. We found that lycorine inhibits proliferation and induces apoptosis in MM cells with less sensitivity to the normal B-cell at the same concentrations. We also found that lycorine promisingly inhibits autophagy, the mechanism that MM cells use to survive and defeat treatment. We identified HMGB1, an important regulator of autophagy, as the most aberrantly expressed protein after lycorine treatment. Furthermore, we characterized HMGB1 as a critical mediator of lycorine activity against MM. Gene expression profiling (GEP) analysis showed that higher expression of HMGB1 is linked with the poor prognosis of MM. We further confirmed this correlation in human bone marrow CD138+ primary myeloma cells and MM cell lines. Mechanistically, by activating the proteasomal degradation of HMGB1, lycorine induces a rapid turnover of HMGB1. This led to decreased Bcl-2 phosphorylation by MEK-ERK pathway and increased association of Bcl-2 with Beclin-1 resulting in autophagy inhibition and growth attenuation. In addition, we observed higher HMGB1 expression in bortezomib resistant cells. The combination of bortezomib plus lycorine was highly efficient against MM cells and MM cells grown in bone marrow micro-environment. Lycorine showed the capability of inhibiting bortezomib induced autophagy as well as re-sensitizing resistant cells to bortezomib. In agreement with our in vitro observations, in vivo study using human MM xenograft model showed that lycorine is well tolerated, inhibits HMGB1 expression and thereby autophagy and induces enhanced bortezomib activity. These observations indicated lycorine as an effective autophagy inhibitor and revealed that lycorine alone or in combination with bortezomib is a potential therapeutic strategy. Our study supports the feasibility of lycorine in anti-MM treatment and provides a preclinical framework for combining lycorine with bortezomib in clinical setting. Disclosures No relevant conflicts of interest to declare.

scholarly journals Recombinant gibbon interleukin-3 acts synergistically with recombinant human G-CSF and GM-CSF in vitro

Blood ◽  
1988 ◽  
Vol 71 (6) ◽  
pp. 1596-1600 ◽  
Author(s):  
RL Paquette ◽  
JY Zhou ◽  
YC Yang ◽  
SC Clark ◽  
HP Koeffler
Keyword(s):  
Colony Formation ◽  
Clinical Utility ◽  
Bone Marrow Cells ◽  
Soft Agar ◽  
Interleukin 3 ◽  
Gm Csf ◽  
Normal Human ◽  
Stimulating Factor ◽  
Normal Human Bone Marrow

Abstract Recombinant gibbon interleukin-3 (IL-3) is a multilineage hematopoietic colony-stimulating factor (CSF) that recently was cloned and found to be highly homologous with human IL-3. Gibbon IL-3, as well as human granulocyte-CSF (G-CSF) and human granulocyte-macrophage CSF (GM-CSF), stimulated normal human bone marrow cells to form myeloid colonies in soft agar in a sigmoidal dose-response manner. When IL-3 was added to increasing concentrations of G-CSF or GM-CSF, synergistic colony formation occurred as compared with the effects of each CSF alone. Synergism was also noted when G-CSF was added with GM-CSF and when all the CSFs were added simultaneously. The combination of IL-3 and GM-CSF was less stimulatory than all the other CSF combinations. At day 11 of culture, IL-3 induced granulocyte-macrophage (38%), eosinophil (30%), granulocyte (18%), and macrophage (14%) colony formation. In summary, gibbon IL-3 is a growth factor that can synergize with other CSFs to enhance proliferation of myeloid-committed progenitors, suggesting that combinations of CSFs may have clinical utility in patients with neutropenia of various etiologies.

scholarly journals Oncogenic lncRNA ZNF561-AS1 is essential for colorectal cancer proliferation and survival through regulation of miR-26a-3p/miR-128-5p-SRSF6 axis

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Zizhen Si ◽  
Lei Yu ◽  
Haoyu Jing ◽  
Lun Wu ◽  
Xidi Wang
Keyword(s):  
Colorectal Cancer ◽  
Rna Binding ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Cancer Proliferation ◽  
Mouse Xenograft ◽  
Mouse Xenograft Model

Abstract Background Long non-coding RNAs (lncRNA) are reported to influence colorectal cancer (CRC) progression. Currently, the functions of the lncRNA ZNF561 antisense RNA 1 (ZNF561-AS1) in CRC are unknown. Methods ZNF561-AS1 and SRSF6 expression in CRC patient samples and CRC cell lines was evaluated through TCGA database analysis, western blot along with real-time PCR. SRSF6 expression in CRC cells was also examined upon ZNF561-AS1 depletion or overexpression. Interaction between miR-26a-3p, miR-128-5p, ZNF561-AS1, and SRSF6 was examined by dual luciferase reporter assay, as well as RNA binding protein immunoprecipitation (RIP) assay. Small interfering RNA (siRNA) mediated knockdown experiments were performed to assess the role of ZNF561-AS1 and SRSF6 in the proliferative actives and apoptosis rate of CRC cells. A mouse xenograft model was employed to assess tumor growth upon ZNF561-AS1 knockdown and SRSF6 rescue. Results We find that ZNF561-AS1 and SRSF6 were upregulated in CRC patient tissues. ZNF561-AS1 expression was reduced in tissues from treated CRC patients but upregulated in CRC tissues from relapsed patients. SRSF6 expression was suppressed and enhanced by ZNF561-AS1 depletion and overexpression, respectively. Mechanistically, ZNF561-AS1 regulated SRSF6 expression by sponging miR-26a-3p and miR-128-5p. ZNF561-AS1-miR-26a-3p/miR-128-5p-SRSF6 axis was required for CRC proliferation and survival. ZNF561-AS1 knockdown suppressed CRC cell proliferation and triggered apoptosis. ZNF561-AS1 depletion suppressed the growth of tumors in a model of a nude mouse xenograft. Similar observations were made upon SRSF6 depletion. SRSF6 overexpression reversed the inhibitory activities of ZNF561-AS1 in vivo, as well as in vitro. Conclusion In summary, we find that ZNF561-AS1 promotes CRC progression via the miR-26a-3p/miR-128-5p-SRSF6 axis. This study reveals new perspectives into the role of ZNF561-AS1 in CRC.

scholarly journals SMAD1 as a biomarker and potential therapeutic target in drug-resistant multiple myeloma

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Jian Wu ◽  
Min Zhang ◽  
Omar Faruq ◽  
Eldad Zacksenhaus ◽  
Wenming Chen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Drug Resistance ◽  
Therapeutic Target ◽  
Biological Activities ◽  
Xenograft Model ◽  
Myeloma Cell ◽  
Soft Agar ◽  
Drug Resistant ◽  
Migration Assay

Abstract Background SMAD1, a central mediator in TGF-β signaling, is involved in a broad range of biological activities including cell growth, apoptosis, development and immune response, and is implicated in diverse type of malignancies. Whether SMAD1 plays an important role in multiple myeloma (MM) pathogenesis and can serve as a therapeutic target are largely unknown. Methods Myeloma cell lines and primary MM samples were used. Cell culture, cytotoxicity and apoptosis assay, siRNA transfection, Western blot, RT-PCR, Soft-agar colony formation, and migration assay, Chromatin immunoprecipitation (Chip), animal xenograft model studies and statistical analysis were applied in this study. Results We demonstrate that SMAD1 is highly expressed in myeloma cells of MM patients with advanced stages or relapsed disease, and is associated with significantly shorter progression-free and overall survivals. Mechanistically, we show that SMAD1 is required for TGFβ-mediated proliferation in MM via an ID1/p21/p27 pathway. TGF-β also enhanced TNFα-Induced protein 8 (TNFAIP8) expression and inhibited apoptosis through SMAD1-mediated induction of NF-κB1. Accordingly, depletion of SMAD1 led to downregulation of NF-κB1 and TNFAIP8, resulting in caspase-8-induced apoptosis. In turn, inhibition of NF-κB1 suppressed SMAD1 and ID1 expression uncovering an autoregulatory loop. Dorsomorphin (DM), a SMAD1 inhibitor, exerted a dose-dependent cytotoxic effect on drug-resistant MM cells with minimal cytotoxicity to normal hematopoietic cells, and further synergized with the proteasomal-inhibitor bortezomib to effectively kill drug-resistant MM cells in vitro and in a myeloma xenograft model. Conclusions This study identifies SMAD1 regulation of NF-κB1/TNFAIP8 and ID1-p21/p27 as critical axes of MM drug resistance and provides a potentially new therapeutic strategy to treat drug resistance MM through targeted inhibition of SMAD1.

scholarly journals Investigations on the Role of the MicroRNA-338-5p/Wnt Family Member 2B (WNT2B) Axis in Regulating the Pathogenesis of Nasopharyngeal Carcinoma (NPC)

2021 ◽  
Vol 11 ◽  
Author(s):  
Suzhen Wang ◽  
Tianning Yang ◽  
Zhengxiang He
Keyword(s):  
Family Member ◽  
Colony Formation ◽  
Epithelial Mesenchymal Transition ◽  
Colony Formation Assay ◽  
Transwell Assay ◽  
Mesenchymal Transition ◽  
Downstream Target

BackgroundThe involvement of microRNA-338-5p in modulating NPC pathogenesis is still largely unknown, and this study aimed to investigate this issue.MethodsThe expressions of cancer associated genes were determined by Real-Time qPCR and Western Blot, and cell apoptosis was determined by flow cytometer (FCM). CCK-8 assay and colony formation assay were respectively used to determine cell proliferation and colony formation abilities. Transwell assay was used to evaluate cell migration. The expression levels of Ki67 protein in mice tissues were measured by Immunohistochemistry (IHC) assay.ResultsThe present study found that microRNA-338-5p suppressed NPC progression by degrading its downstream target, Wnt family member 2B (WNT2B). Specifically, microRNA-338-5p tended to be low-expressed in NPC tissues and cell lines, compared to the non-tumor nasopharyngeal mucosa tissues and normal nasopharyngeal cell line (NP69). Upregulation of microRNA-338-5p inhibited proliferation, mobility, and epithelial-mesenchymal transition (EMT) in NPC cells in vitro, while silencing of microRNA-338-5p had opposite effects. Consistently, microRNA-338-5p suppressed tumorigenesis of NPC cells in vivo. In addition, microRNA-338-5p targeted WNT2B for degradation and inhibition, and the inhibiting effects of microRNA-338-5p overexpression on NPC development were reversed by upregulating WNT2B.ConclusionsTaken together, we concluded that microRNA-338-5p targeted WNT2B to hinder NPC development.

scholarly journals NUSAP1 Promotes Gastric Cancer Progression Through Regulation of Yap Stability

2020 ◽  
Author(s):  
Hui Guo ◽  
Jianping Zou ◽  
Ling Zhou ◽  
Yan He ◽  
Miao Feng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Target Genes ◽  
Hippo Pathway ◽  
Critical Role ◽  
Xenograft Model ◽  
Migration And Invasion

Abstract Background:Nucleolar and spindle associated protein (NUSAP1) is involved in tumor initiation, progression and metastasis. However, there are limited studies regarding the role of NUSAP1 in gastric cancer (GC). Methods: The expression profile and clinical significance of NUSAP1 in GC were analysed in online database using GEPIA, Oncomine and KM plotter, which was further confirmed in clinical specimens.The functional role of NUSAP1 were detected utilizing in vitro and in vivo assays. Western blotting, qRT-PCR, the cycloheximide-chase, immunofluorescence staining and Co-immunoprecipitaion (Co-IP) assays were performed to explore the possible molecular mechanism by which NUSAP1 stabilizes YAP protein. Results:In this study, we found that the expression of NUSAP1 was upregulated in GC tissues and correlates closely with progression and prognosis. Additionally, abnormal NUSAP1 expression promoted malignant behaviors of GC cells in vitro and in a xenograft model. Mechanistically, we discovered that NUSAP1 physically interacts with YAP and furthermore stabilizes YAP protein expression, which induces the transcription of Hippo pathway downstream target genes. Furthermore, the effects of NUSAP1 on GC cell growth, migration and invasion were mainly mediated by YAP. Conclusions:Our data demonstrates that the novel NUSAP1-YAP axis exerts an critical role in GC tumorigenesis and progression, and therefore could provide a novel therapeutic target for GC treatment.

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