scholarly journals Overexpression of Long Non-Coding RNA NNT-AS1 Correlates with Tumor Progression and Poor Prognosis in Osteosarcoma

2018 ◽  
Vol 45 (5) ◽  
pp. 1904-1914 ◽  
Author(s):  
Hui Ye ◽  
Jinkuang Lin ◽  
Xuedong Yao ◽  
Yizhong Li ◽  
Xiaobin Lin ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Poor Prognosis ◽  
Significant Risk ◽  
Xenograft Model ◽  
Significant Risk Factor ◽  
Tumor Xenograft ◽  
Migration And Invasion ◽  
Mouse Xenograft Model

Background/Aims: Increasing evidence demonstrates that long non-coding RNAs (lncRNAs) play critical regulatory roles in cancers, including osteosarcoma. A previous study showed that Nicotinamide Nucleotide Transhydrogenase-antisense RNA1 (NNT-AS1) was aberrantly expressed in several types of cancer. However, the potential biological roles and regulatory mechanisms of NNT-AS1 in osteosarcoma progression remain unknown. Methods: Quantitative RT-PCR was performed to examine the expression of NNT-AS1 in human tissues and cells. The biological functions of NNT-AS1 were determined by CCK-8, colony formation, Flow cytometry and Transwell assays in vitro. A mouse xenograft model was performed to investigate the effect of NNT-AS1 on tumor growth in vivo. Results: In this study, we found the expression of NNT-AS1 was significantly increased in tumor tissues compared to adjacent normal tissues. Furthermore, upregulated NNT-AS1 expression predicted poor prognosis and was an independent and significant risk factor for osteosarcoma patient survival. Further experiments revealed that NNT-AS1 knockdown significantly inhibited cell proliferation by inducing cell cycle arrest and promoting apoptosis in osteosarcoma cells. Moreover, NNT-AS1 silencing suppressed cell migration and invasion in vitro. In a tumor xenograft model, knockdown of NNT-AS1 suppressed tumor growth of OS-732 cells in vivo. Conclusions: Taken together, these findings indicate that NNT-AS1 functions as an oncogene in osteosarcoma and could be a novel diagnostic and therapeutic target for osteosarcoma.

scholarly journals Hypoxia-regulated expression of CD44 and osteopontin can change the phenotype of glioma stem-like cells from highly invasive to less invasive/proliferative tumors in glioblastoma

2020 ◽  
Author(s):  
Masahiro Nishikawa ◽  
Akihiro Inoue ◽  
Takanori Ohnishi ◽  
Hajime Yano ◽  
Saya Ozaki ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Xenograft Model ◽  
Migration And Invasion ◽  
Invasive Phenotype ◽  
Moderate Hypoxia ◽  
Less Invasive ◽  
Mouse Xenograft Model ◽  
Phenotypic Transition

Abstract Background The poor prognosis of glioblastoma multiforme (GBM) is primarily due to highly invasive and highly migratory glioma stem-like cells (GSCs) in tumors. Upon GBM recurrence or progression, the highly invasive phenotype of GSCs changes to a less-motile, proliferative phenotype, thus generating tumor mass. Elucidating the molecular mechanism underlying this phenotypic transition could lead to the identification of effective molecular targets for treating GBM. Methods We examined mRNA expression of hypoxia-inducible factor (HIF)-1α, HIF-2α, CD44, and osteopontin in GBM tissues and investigated the effect of hypoxia (1% O2: severe or 5% O2: moderate) on expression of these molecules using two lines of cultured GSCs. We also analyzed the effect of osteopontin on the invasiveness, migration, and proliferation of GSCs under hypoxic conditions. In addition, the effect of CD44 knockdown on tumor growth and survival were investigated in vitro and in vivo using a mouse xenograft model. Results Severe hypoxia upregulates CD44 expression via activation of HIF-1α, inducing GSCs to assume a highly invasive phenotype. In contrast, moderate hypoxia upregulates osteopontin expression via activation of HIF-2α. Osteopontin in turn binds to CD44, simultaneously inhibiting CD44-promoted GSC migration and invasion and stimulating GSC proliferation, resulting in GSCs assuming a less-invasive, highly proliferative phenotype. CD44 knockdown significantly inhibited GSC migration and invasion both in vitro and in vivo. However, although CD44 knockdown did not affect tumor growth in vitro, mouse brain tumors generated from GSCs with CD44 knockdown exhibited diminished invasiveness, and the mice survived significantly longer than control mice. In contrast, siRNA-mediated silencing of the osteopontin gene led to decreased GSC proliferation, but the osteopontin-mediated inhibition of high GSC migratory behavior and invasiveness was diminished. Conclusion The highly invasive phenotype of GSCs can be reversed by switching from severe to moderate hypoxia, leading to less-invasive and proliferative tumors. CD44 and osteopontin, which are expressed in a mutually exclusive manner under severe or moderate hypoxia, play a central role in regulating GSC invasion and proliferation by inducing a phenotypic transition, suggesting that these molecules could be effective targets for treating both primary and recurrent GBM.

scholarly journals RETRACTED ARTICLE: α2,6-Sialylation mediates hepatocellular carcinoma growth in vitro and in vivo by targeting the Wnt/β-catenin pathway

Oncogenesis ◽  
2017 ◽  
Vol 6 (5) ◽  
pp. e343-e343 ◽  
Author(s):  
Y Zhao ◽  
A Wei ◽  
H Zhang ◽  
X Chen ◽  
L Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Poor Prognosis ◽  
Xenograft Model ◽  
Migration And Invasion ◽  
Mouse Xenograft Model ◽  
Retracted Article ◽  
Underlying Mechanisms ◽  
St6gal I

Abstract Abnormal sialylation due to overexpression of sialyltransferases has been associated with tumorigenesis and tumor progression. Although ST6Gal-I influences cancer persistence and progression by affecting various receptors, the underlying mechanisms and mediators remain largely obscure, especially in hepatocellular carcinoma (HCC). We found that ST6Gal-I expression was markedly upregulated in HCC tissues and cells, high levels being associated with aggressive phenotype and poor prognosis. Furthermore, we examined the roles and mechanisms of ST6Gal-I in HCC tumorigenesis and metastasis in vitro and in vivo. ST6Gal-I overexpression promoted proliferation, migration and invasion of Huh-7 cells, whereas its knockdown restricted these abilities in MHCC97-H cells. Additionally, in a mouse xenograft model, ST6Gal-I-knockdown MHCC97-H cells formed significantly smaller tumors, implying that ST6Gal-I overexpression can induce HCC cell malignant transformation. Importantly, enhanced HCC tumorigenesis and metastasis by ST6Gal-I may be associated with Wnt/β-catenin signaling promotion, including β-catenin nuclear transition and upregulation of downstream molecules. Together, our results suggest a role for ST6Gal-I in promoting the growth and invasion of HCC cells through the modulation of Wnt/β-catenin signaling molecules, and that ST6Gal-I might be a promising marker for prognosis and therapy of HCC.

scholarly journals MNAT1 promotes proliferation and the chemo-resistance of osteosarcoma cell to cisplatin through regulating PI3K/Akt/mTOR pathway

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Chensheng Qiu ◽  
Weiliang Su ◽  
Nana Shen ◽  
Xiaoying Qi ◽  
Xiaolin Wu ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Xenograft Model ◽  
Mtor Pathway ◽  
Regulation Mechanism ◽  
Osteosarcoma Cell ◽  
Migration Ability ◽  
Mouse Xenograft Model

Abstract Background MNAT1 (menage a trois 1, MAT1), a cyclin-dependent kinase-activating kinase (CAK) complex, highly expressed in diverse cancers and was involved in cancer molecular pathogenesis. However, its deliverance profile and biological function in osteosarcoma (OS) remain unclear. Methods The expression of MNAT1 in OS was detected by western blot (WB) and immunohistochemistry (IHC). The potential relationship between MNAT1 molecular level expression and OS clinical expectations were analyzed according to tissues microarray (TMA). Proliferation potential of OS cells was evaluated in vitro based on CCK8 and OS cells colony formation assays, while OS cells transwell and in situ tissue source wound healing assays were employed to analyze the OS cells invasion and migration ability in vitro. A nude mouse xenograft model was used to detect tumor growth in vivo. In addition, ordinary bioinformatics analysis and experimental correlation verification were performed to investigate the underlying regulation mechanism of OS by MNAT1. Results In this research, we found and confirmed that MNAT1 was markedly over-expressed in OS tissue derived in situ, also, highly MNAT1 expression was closely associated with bad clinical expectations. Functional studies had shown that MNAT1 silencing could weaken the invasion, migration and proliferation of OS cells in vitro, and inhibit OS tumor growth in vivo. Mechanism study indicated that MNAT1 contributed to the progression of OS via the PI3K/Akt/mTOR pathway. We further verified that the MNAT1 was required in the regulation of OS chemo-sensitivity to cisplatin (DDP). Conclusions Taken together, the data of the present study demonstrate a novel molecular mechanism of MNAT1 involved in the formation of DDP resistance of OS cells.

scholarly journals TRIM33 Overexpression Inhibits the Progression of Clear Cell Renal Cell Carcinoma In Vivo and In Vitro

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Yingkun Xu ◽  
Guangzhen Wu ◽  
Jiayao Zhang ◽  
Jianyi Li ◽  
Ningke Ruan ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Mrna Expression ◽  
Wnt Signaling Pathway ◽  
Xenograft Model ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Cell Renal Cell Carcinoma ◽  
Expression Levels

Purpose. To evaluate the expression of tripartite motif-containing 33 (TRIM33) in ccRCC tissues and explore the biological effect of TRIM33 on the progress of ccRCC. Method. The Cancer Genome Atlas (TCGA) database was used to examine the mRNA expression levels of TRIM33 in ccRCC tissues and its clinical relevance. Immunohistochemistry (IHC) was performed to evaluate its expression in ccRCC tissues obtained from our hospital. The correlation between TRIM33 expression and clinicopathological features of the patients was also investigated. The effects of TRIM33 on the proliferation of ccRCC cells were examined using the CCK-8 and colony formation assays. The effects of TRIM33 on the migration and invasion of ccRCC cells were explored through wound healing and transwell assays, along with the use of Wnt signaling pathway agonists in rescue experiments. Western blotting was used to explore the potential mechanism of TRIM33 in renal cancer cells. A xenograft model was used to explore the effect of TRIM33 on tumor growth. Result. Bioinformatics analysis showed that TRIM33 mRNA expression in ccRCC tissues was downregulated, and low TRIM33 expression was related to poor prognosis in ccRCC patients. In agreement with this, low TRIM33 expression was detected in human ccRCC tissues. TRIM33 expression levels were correlated with clinical characteristics, including tumor size and Furman’s grade. Furthermore, TRIM33 overexpression inhibited proliferation, migration, and invasion of 786-O and ACHN cell lines. The rescue experiment showed that the originally inhibited migration and invasion capabilities were restored. TRIM33 overexpression reduced the expression levels of β-catenin, cyclin D1, and c-myc, and inhibited tumor growth in ccRCC cells in vivo. Conclusion. TRIM33 exhibits an abnormally low expression in human ccRCC tissues. TRIM33 may serve as a potential therapeutic target and prognostic marker for ccRCC.

scholarly journals Distinct inhibitory efficiency of siRNAs and DNAzymes to β1 integrin subunit in blocking tumor growth.

2013 ◽  
Vol 60 (1) ◽  
Author(s):  
Magdalena Wiktorska ◽  
Izabela Sacewicz-Hofman ◽  
Olga Stasikowska-Kanicka ◽  
Marian Danilewicz ◽  
Jolanta Niewiarowska
Keyword(s):  
Tumor Growth ◽  
Xenograft Model ◽  
Tumor Formation ◽  
Integrin Subunit ◽  
Β1 Integrin ◽  
Mouse Xenograft ◽  
Mouse Xenograft Model ◽  
Intracellular Compartments

Receptors of the β1 integrin family are involved in many tumor-promoting activities. There are several approaches currently used to control integrin activity, and thus to potentially restrain tumor metastasis and angiogenesis. In this study, we compared inhibitory efficiencies of siRNA and DNAzymes against the β1 integrin subunit (DEβ1), in a mouse xenograft model. Both inhibitors were used under their most favorable conditions, in terms of concentrations, incubation time and lack of cytotoxic effects. Transfection of siRNAβ1 or DEβ1 remarkably inhibited the growth of both PC3 and HT29 colon cancer cells in vitro, and decreased their capability of initiating tumor formation in the mouse xenograft model. siRNAβ1 appeared to be slightly more efficient than DEβ1 when tested in vitro, however it was comparably less proficient in blocking the tumor growth in vivo. We conclude the DNAzyme, due to its greater resistance to degradation in extra- and intracellular compartments, to be a superior inhibitor of tumor growth in long lasting experiments in vivo when compared to siRNA, while the latter seems to be more efficient in blocking β1 expression during in vitro experiments using cell cultures.

scholarly journals Long Non-Coding RNA NEAT1 Promotes HCC Progression via PKM2 and Exosome-Mediated Transfer

2021 ◽  
Author(s):  
Junping Pan ◽  
Yingzhe Hu ◽  
Chenlu Yuan ◽  
Yafu Wu ◽  
Xinhua Zhu
Keyword(s):  
Malignant Tumors ◽  
Xenograft Model ◽  
Migration And Invasion ◽  
Mouse Xenograft Model ◽  
Rna Immunoprecipitation ◽  
Tumor Growth And Metastasis ◽  
Lncrna Neat1 ◽  
Hcc Cells

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with high mortality and poor prognosis. Long non-coding RNAs NEAT1 (lncRNA NEAT1) have been found to play an important role in HCC progression. However, the role and potential molecular mechanism of lncRNA NEAT1 in HCC remain largely unclear. Methods The role of lncRNA NEAT1 both in vitro and in vivo was investigated, with RNA pull-down and RNA immunoprecipitation (RIP) assays being performed to determine the interaction among NEAT1 and FOXO3 and PKM2. In addition, HCC cells were treated with exosomes derived from NEAT1-overexpressing HCC cells, and then cell proliferation, migration and invasion were assessed using in vitro assays. Results In this study, overexpression of NEAT1 promoted the proliferation, migration and invasion of HCC cells, whereas NEAT1 knockdown exhibited the opposite effects. Mechanistically, NEAT1 was found to recruit transcription factor FOXO3 to PKM2 promoter region and upregulate PKM2 expression. Meanwhile, overexpression of NEAT1 increased tumor growth and metastasis in a mouse xenograft model of HCC in vivo via upregulation of PKM2. Furthermore, overexpression of NEAT1 promoted exosome release from HCC cells. Exosomes secreted from NEAT1-overexpressing HCC cells promoted the proliferation, migration and invasion of HCC cells. Conclusion We found that NEAT1 could promote HCC progression via upregulation of PKM2 and exosome-mediated transfer. These data indicated that NEAT1 may be a therapeutic target in HCC.

scholarly journals Calmodulin 2 Facilitates Angiogenesis and Metastasis of Gastric Cancer via STAT3/HIF-1A/VEGF-A Mediated Macrophage Polarization

2021 ◽  
Vol 11 ◽  
Author(s):  
Ganggang Mu ◽  
Yijie Zhu ◽  
Zehua Dong ◽  
Lang Shi ◽  
Yunchao Deng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Growth ◽  
Lung Metastasis ◽  
Macrophage Polarization ◽  
Xenograft Model ◽  
Migration And Invasion ◽  
Tubule Formation ◽  
Set Up

BackgroundTumor-associated macrophages (TAMs) are indispensable to mediating the connections between cells in the tumor microenvironment. In this study, we intended to research the function and mechanism of Calmodulin2 (CALM2) in gastric cancer (GC)-TAM microenvironment.Materials and methodsCALM2 expression in GC tissues and GC cells was determined through quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC). The correlation between CALM2 level and the survival rate of GC patients was assessed. The CALM2 overexpression or knockdown model was constructed to evaluate its role in GC cell proliferation, migration, and invasion. THP1 cells or HUVECs were co-cultured with the conditioned medium of GC cells. Tubule formation experiment was done to examine the angiogenesis of endothelial cells. The proliferation, migration, and polarization of THP1 cells were measured. A xenograft model was set up in BALB/c male nude mice to study CALM2x’s effects on tumor growth and lung metastasis in vivo. Western Blot (WB) checked the profile of JAK2/STAT3/HIF-1/VEGFA in GC tissues and cells.ResultsIn GC tissues and cell lines, CALM2 expression was elevated and positively relevant to the poor prognosis of GC patients. In in-vitro experiments, CALM2 overexpression or knockdown could facilitate or curb the proliferation, migration, invasion, and angiogenesis of HUVECs and M2 polarization of THP1 cells. In in-vivo experiments, CALM2 boosted tumor growth and lung metastasis. Mechanically, CALM2 could arouse the JAK2/STAT3/HIF-1/VEGFA signaling. It was also discovered that JAK2 and HIF-1A inhibition could attenuate the promoting effects of CALM2 on GC, HUVECs cells, and macrophages.ConclusionCALM2 modulates the JAK2/STAT3/HIF-1/VEGFA axis and bolsters macrophage polarization, thus facilitating GC metastasis and angiogenesis.

scholarly journals Hsa_circ_0026416 promotes proliferation and migration in colorectal cancer via miR-346/NFIB axis

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yahang Liang ◽  
Jingbo Shi ◽  
Qingsi He ◽  
Guorui Sun ◽  
Lei Gao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Molecular Mechanisms ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Potential Biomarker ◽  
Mouse Xenograft Model

Abstract Background Colorectal cancer (CRC) is one of the most common cancers worldwide. Circular RNAs (circRNAs), a novel class of non-coding RNAs, have been confirmed to be key regulators of many diseases. With many scholars devoted to studying the biological function and mechanism of circRNAs, their mysterious veil is gradually being revealed. In our research, we explored a new circRNA, hsa_circ_0026416, which was identified as upregulated in CRC with the largest fold change (logFC = 3.70) of the evaluated circRNAs via analysing expression profiling data by high throughput sequencing of members of the GEO dataset (GSE77661) to explore the molecular mechanisms of CRC. Methods qRT-PCR and western blot analysis were utilized to assess the expression of hsa_circ_0026416, miR-346 and Nuclear Factor I/B (NFIB). CCK-8 and transwell assays were utilized to examine cell proliferation, migration and invasion in vitro, respectively. A luciferase reporter assay was used to verify the combination of hsa_circ_0026416, miR-346 and NFIB. A nude mouse xenograft model was also utilized to determine the role of hsa_circ_0026416 in CRC cell growth in vivo. Results Hsa_circ_0026416 was markedly upregulated in CRC patient tissues and plasma and was a poor prognosis in CRC patients. In addition, the area under the curve (AUC) of hsa_circ_0026416 (0.767) was greater than the AUC of CEA (0.670), CA19-9 (0.592) and CA72-4 (0.575). Functionally, hsa_circ_0026416 promotes cell proliferation, migration and invasion both in vitro and in vivo. Mechanistically, hsa_circ_0026416 may function as a ceRNA via competitively absorbing miR-346 to upregulate the expression of NFIB. Conclusions In summary, our findings demonstrate that hsa_circ_0026416 is an oncogene in CRC. Hsa_circ_0026416 promotes the progression of CRC via the miR-346/NFIB axis and may represent a potential biomarker for diagnosis and therapy in CRC.

scholarly journals Identification and characterization of a subpopulation of CD133+ cancer stem‐like cells derived from SK-UT-1 cells

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jiuping Gao ◽  
Ting Yang ◽  
Xu Wang ◽  
Yi Zhang ◽  
Jing Wang ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Population ◽  
Colony Formation ◽  
Xenograft Model ◽  
Migration And Invasion ◽  
Uterine Leiomyosarcoma ◽  
Tumorigenic Potential ◽  
Mouse Xenograft Model

Abstract Background Uterine leiomyosarcoma (ULMS) is a malignant tumor found in the smooth muscle lining the walls of the uterus. Cancer stem cells (CSCs) are responsible for metastasis, drug resistance, and relapse of cancer, resulting in treatment failure. However, little is known about CSCs and their associated-markers in ULMS. We aimed to characterize and identify a subpopulation of CD133+ cancer stem-like cells derived from SK-UT-1 cell line. Methods SK-UT-1 cells were sphere-forming cultured in vitro. We also sorted the CD133+ cells derived from SK-UT-1 cell line by immunomagnetic beads. CD133+ subpopulation and apoptotic cells were detected by flow cytometry. Self-renewal and anchorage-independent growth capabilities were examined using sphere and colony formation assays. The tumorigenicity of the fourth-passage spheres and parental SK-UT-1 cells was used by mouse xenograft model in vivo. Cell proliferation ability and sensitivity to doxorubicin (DXR) were assessed by CCK-8 assay. Cell migration and invasion were tested by wound healing assay or Transwell migration and invasion assays. Expressions of CSC-related marker were analyzed by Western blotting. Results The fourth-passage spheres were defined as a CD133+ cell population, which was accompanied by increase of sphere and colony forming rate, migration and invasion abilities, as well as drug-resistant properties in vitro. Moreover, the fourth-passage spheres showed a stronger tumorigenic potential in vivo. CD133+ cell population sorted from SK-UT-1 line showed an increased ability in sphere and colony formation, proliferation, migration, invasion, resistance to apoptosis after treatment with doxorubicin (DXR) compared with CD133− cell population. The expression levels of CSCs-related markers (e.g., CD44, ALDH1,BMI1, and Nanog), were significantly elevated in CD133+ cells compared with those in CD133− cells. Conclusions Collectively, our findings indicated that CD133 may be a significant marker for cancer stem-like cells, and it may be a potential therapeutic target for human ULMS.

MicroRNA-760 inhibits cell viability and migration through down-regulating BST2 in gastric cancer

2020 ◽  
Vol 168 (2) ◽  
pp. 159-170
Author(s):  
Weiyu Liu ◽  
Yan Li ◽  
Shuting Feng ◽  
Yadi Guan ◽  
Yong Cao
Keyword(s):  
Gastric Cancer ◽  
Cell Viability ◽  
Primary Tumour ◽  
Xenograft Model ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Mouse Xenograft Model ◽  
Cancer Tissues

Abstract Gastric cancer is one of the most common types of carcinoma with a threat to global health. MicroRNA-760 (miR-760) was significantly down-regulated in the primary tumour of patients with advanced gastric cancer. However, the role of miR-760 in gastric cancer is still unclear. Herein, miR-760 was down-regulated in gastric cancer tissues. Moreover, miR-760 overexpression and knockdown were conducted in gastric cancer cells (MGC-803 and SGC-7901) in vitro. The in vitro functional assays proved that miR-760 overexpression reduced cell viability, cell cycle, migration and invasion, promoted apoptosis and suppressed MMP activity in MGC-803 cells. Conversely, miR-760 knockdown led to the opposite in SGC-7901 cells. Notably, bone marrow stromal antigen 2 (BST2) was verified as a target gene of miR-760. MiR-760 mimics down-regulated BST2 level in gastric cancer tissues and in MGC-803 cells, whereas miR-760 inhibitor up-regulated its level in SGC-7901 cells. MiR-760-regulated cell properties through reduction of BST2. In addition, miR-760 inhibited tumourigenesis in a nude mouse xenograft model in vivo. In conclusion, our results demonstrated that miR-760 exhibited a suppressive role in gastric cancer via inhibiting BST2, indicating that miR-760/BST2 axis may provide promising therapeutic target for gastric cancer.

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