scholarly journals PYCR1 Promotes Proliferation, Invasion and Drug-Resistance of Lung Cancer Cells by Regulating STAT3-Mediated PI3K/AKT and NF-κB Signaling Pathway

2020 ◽  
Author(s):  
Zhanwu Yu ◽  
Gebang Wang ◽  
Chenlei Zhang ◽  
Yu Liu ◽  
Wei Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Target Genes ◽  
Western Blot Assay ◽  
Aberrant Expression ◽  
Efficient Treatment ◽  
Underlying Mechanisms

Abstract Background: Aberrant expression of PYCR1 has been proved to be one of the most pivotal regulators of tumor progress and metastasis. However, the detailed role of PYCR1 in promotion of NSCLC progress is not investigated thoroughly. The present study was aimed to thoroughly investigate the effect of PYCR1 in the growth of NSCLC and the underlying mechanisms, so that provide valuable theoretical basis for efficient treatment of NSCLC. Methods: The expressions of PYCR1 and its target genes and downstream signals were respectively determined by Western-blot assay and RT-qPCR experiment. Cell growth of NSCLC cells was investigated using the CCK-8 kit while the proliferation assay was performed with the help of EDU staining. The NSCLC-bearing mice mode was established to evaluate the effect of PYCR1 on the progress of NSCLC and the underlying mechanisms in vivo.Results: It was firstly demonstrated that the PYCR1 was overexpressed in lung cancer tissues and cells and overexpression of PYCR1 contributed to significantly enhanced proliferation, invasion, and drug-resistance of cancer cells and progress of NSCLC tissues. Further studies revealed that up-regulation of PYCR1 level resulted to the elevation of bioactivity of STAT3. Additionally, the positive correlation between the expression of PYCR1 and STAT3 indicated that the PYCR1 promotes the growth of NSCLC through targeting regulation the STAT3 levels. Furthermore, activation of STAT3 by PYCR1 was proved to be able of awaking the PI3K/AKT and NF-κB signaling pathway, which was extremely important to the metabolism, proliferation, cell survival, and growth of many cancer cell types.Conclusion: In conclusion, our study demonstrated that PYCR1 was specifically overexpressed in lung cancer and closely related to rapid progress and drug-resistance thorough regulating the STAT3-mediated PI3K/AKT and NF-κB signaling pathway. It may provide a valuable strategy for treatment of malignant lung cancer.

Long non coding RNA CCAT2 enhances proliferation, invasion and drug-resistances of non-small lung cancer via activating the miR-204-3p-suppresed IGFBP2/AKT/Bcl2 pathway

2020 ◽  
Author(s):  
Zheng Wang ◽  
Rongjie Yang ◽  
Yu Liu ◽  
Yanfeng Huang
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Theoretical Basis ◽  
High Rate ◽  
Aberrant Expression ◽  
Efficient Treatment ◽  
Non Coding Rna ◽  
Tumor Tissues ◽  
Underlying Mechanisms ◽  
Long Non Coding Rna

Abstract Background The treatment efficacy remains unsatisfactory due to the rapid progress, high rate of metastasis, and drug-resistance of NSCLS. It has been demonstrated that aberrant expression of long non coding RNA colon cancer-associated transcript 2 (CCAT2) in cells was closely related to tumorigenesis, tumor metastasis, and development of drug-resistance. The present study was aimed to thoroughly investigate the effect of CCAT2 in the growth of NSCLC and the underlying mechanisms, so that provide valuable theoretical basis for efficient treatment of NSCLC. Methods The expressions of CCAT2 and its target genes and downstream signals were respectively determined by Western-blot assay and RT-qPCR experiment. Cell growth of NSCLC cells was investigated using the CCK-8 kit while the proliferation assay was performed with the help of EDU staining. The NSCLC-bearing mice mode was established to evaluate the effect of PYCR1 on the progress of NSCLC and the underlying mechanisms in vivo. Results The CCAT2 was highly expressed in NSCLC tumor tissues and cells while not the corresponding normal ones. Further studies revealed that aberrant expression of CCAT2 in lung cancer signally contributed to proliferation, invasion, and migration of cancer cells and the progress of tumor tissues. Moreover, high level of CCAT2 dramatically down-regulated the cytotoxicity of cisplatin (DDP) to NSCLC cells and tissues by upregulation of the drug-resistance related proteins. Mechanisms studies displayed that upregulation of CCAT2 markedly decreased the miR-204-3p while contrary result was obtained when down-regulated the CCAT2 level. We further demonstrated that down-regulation of miR-204-3p level signally enhanced the activity of the insulin-like growth factor (IGF) signaling pathway. Conclusions The CCAT2 promoted the progress and drug-resistance of NSCLC thorough activation of the miR-204-3p suppressed IGFBP2/AKT/Bcl2 pathway, and may provide theoretical basis for improvement of therapy of NSCLC.

scholarly journals Long non coding RNA CCAT2 enhances the proliferation, migration, invasion and drug-resistances of non-small lung cancer via activating the miR-204-3p-suppresed IGFBP2/AKT/Bcl2 pathway

2020 ◽  
Author(s):  
Zheng Wang ◽  
Rongjie Yang ◽  
Yu Liu ◽  
Yanfeng Huang
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Theoretical Basis ◽  
High Rate ◽  
Aberrant Expression ◽  
Efficient Treatment ◽  
Non Coding Rna ◽  
Underlying Mechanisms ◽  
Long Non Coding Rna ◽  
Qpcr Experiment

Abstract Background: To date, the treatment efficacy of NSCLC remains unsatisfactory mainly ascribed to the rapid progress, high rate of metastasis, and emerged drug-resistance. It has been demonstrated that aberrant expression of long non coding RNA colon cancer-associated transcript 2 (CCAT2) was closely related to tumorigenesis and development of drug-resistance of many cancer types. The present study was aimed to thoroughly investigate the effect of CCAT2 in the progress of NSCLC and the underlying mechanisms, so that provide valuable theoretical basis for efficient treatment of NSCLC.Methods: The expressions of CCAT2 were determined using the RT-qPCR experiment. Its target genes and downstream molecules were respectively evaluated by Western-blot assay and RT-qPCR experiment. Cell growth of NSCLC cells was investigated using the CCK-8 kit. The effect of CCAT2 on the progress of NSCLC and the underlying mechanisms in vivo was determined on the NSCLC-bearing mice models.Results: Higher expression of CCAT2 was detected in the lung cancer tissues and cells than the normal ones. Moreover, it was revealed that aberrant expression of CCAT2 in lung cancer signally contributed to proliferation, invasion, and migration of cancer cells and the progress of tumor tissues. Additionally, high level of CCAT2 dramatically down-regulated the cytotoxicity of cisplatin (DDP) to NSCLC cells and tissues by upregulation of the drug-resistance related proteins. Mechanisms studies displayed that upregulation of CCAT2 markedly decreased the miR-204-3p while contrary result was obtained when down-regulated the CCAT2 level. We further demonstrated that down-regulation of miR-204-3p level signally enhanced the activity of the insulin-like growth factor (IGF) signaling pathway.Conclusions: The CCAT2 promoted the progress and drug-resistance of NSCLC thorough activation of the miR-204-3p suppressed IGFBP2/AKT/Bcl2 pathway, and may provide theoretical basis for improvement of therapy of NSCLC.

scholarly journals LncRNA SNHG7 Regulates Mesenchymal Stem Cell Through the Notch1/Jagged1/Hes-1 Signaling Pathway and Influences Folfirinox Resistance in Pancreatic Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Dongfeng Cheng ◽  
Juanjuan Fan ◽  
Kai Qin ◽  
Yiran Zhou ◽  
Jingrui Yang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Resistance Development ◽  
Pancreatic Cancer Cells ◽  
Novel Approach ◽  
Sphere Formation

Pancreatic cancer (PC) is one of the deadliest gastrointestinal cancers, accounting for the fourth highest number of cancer-related fatalities. Increasing data suggests that mesenchymal stem cells (MSCs) might influence the drug resistance of GC cells in the tumor microenvironment and play essential roles in drug resistance development. However, the precise underlying process remains a mystery. The purpose of this study was to look at the control of MSC-induced SNHG7 in pancreatic cancer. In vitro and in vivo sphere formation, colony formation, and flow cytometry investigations revealed the stemness and Folfirinox resistance in pancreatic cancer cells. To confirm the direct connections between SNHG7 and other related targets, RNA pulldown and immunoprecipitation tests were performed. MSC co-culture enhanced the stemness and Folfirinox resistance in pancreatic cancer cells according to the findings. MSC co-culture increased SNHG7 expression in pancreatic cancer cells, contributing to the stemness and Folfirinox resistance. We demonstrated that Notch1 interacted with SNHG7 and could reverse the facilitative effect of SNHG7 on the stemness and Folfirinox resistance in pancreatic cancer cells. Finally, our findings showed that MSCs increased SNHG7 expression in pancreatic cancer cells, promoting the stemness and Folfirinox resistance via the Notch1/Jagged1/Hes-1 signaling pathway. These findings could provide a novel approach and therapeutic target for pancreatic cancer patients.

scholarly journals Bortezomib potentiates antitumor activity of mitoxantrone through dampening Wnt/β-catenin signal pathway in prostate cancer cells

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ying Zhang ◽  
Qiuzi Liu ◽  
Wei Wei ◽  
Guoan Zhang ◽  
Siyuan Yan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Target Genes ◽  
Signal Pathway ◽  
Prostate Cancer Cells ◽  
Anticancer Effects ◽  
Induced Apoptosis

Abstract Background Bortezomib (BZM), alone or in combination with other chemotherapies, has displayed strong anticancer effects in several cancers. The efficacy of the combination of BZM and mitoxantrone (MTX) in treating prostate cancer remains unknown. Methods Anticancer effects of combination of BZM and MTX were determined by apoptosis and proliferation assay in vivo and in vitro. Expression of β-Catenin and its target genes were characterized by western blot and Real-time PCR. Results BZM significantly enhanced MTX-induced antiproliferation in vivo and in vitro. Mice administered a combination of BZM and MTX displayed attenuated tumor growth and prolonged survival. BZM significantly attenuated MTX-induced apoptosis. Moreover, the combination of BZM and MTX contributed to inhibition of the Wnt/β-Catenin signaling pathway compared to monotherapy. Conclusions This study demonstrates that BZM enhances MTX-induced anti-tumor effects by inhibiting the Wnt/β-Catenin signaling pathway in prostate cancer cells.

scholarly journals CircHIPK3/miR-381-3p axis modulates proliferation, migration, and glycolysis of lung cancer cells by regulating the AKT/mTOR signaling pathway

2020 ◽  
Vol 15 (1) ◽  
pp. 683-695
Author(s):  
Feng Gu ◽  
Junhan Zhang ◽  
Lin Yan ◽  
Dong Li
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Mtor Signaling ◽  
Lung Cancer Cells ◽  
Luciferase Reporter ◽  
Mtor Signaling Pathway

AbstractLung cancer is a lethal malignancy. Plenty of circular RNAs (circRNAs) have been identified to be the vital regulators in lung cancer development. Here, we intended to clarify the functional role of circRNA HIPK3 (circHIPK3, also called hsa_circ_0021593) and its underlying mechanism of action. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was employed to evaluate the levels of circHIPK3 and miR-381-3p. Cell viability and apoptosis rate were monitored by Cell Counting Kit-8 assay and flow cytometry, respectively. Cell migration was estimated through the Transwell assay. To assess glycolysis, commercial kits were utilized to measure the levels of glucose and lactate and the enzyme activity of hexokinase-2 (HK2). Expression of related proteins was detected via western blot analysis. The target connection between circHIPK3 and miR-381-3p was validated by dual-luciferase reporter, RIP, and pull-down assays. The role of circHIPK3 in vivo was determined via the xenograft assay. CircHIPK3 was upregulated, while miR-381-3p was downregulated in lung cancer tissues and cells. And circHIPK3 deficiency inhibited lung cancer progression by lowering cell proliferation, migration, glycolysis, and promoting apoptosis of lung cancer cells in vitro. MiR-381-3p was a target of circHIPK3, and miR-381-3p interference alleviated circHIPK3 knockdown-induced lung cancer progression inhibition. CircHIPK3 could activate the protein kinase B/mammalian target of rapamycin (AKT/mTOR) signaling pathway. Moreover, circHIPK3 knockdown suppressed tumor growth in vivo by inactivating the AKT/mTOR signaling pathway. In conclusion, the silencing of circHIPK3 inhibited lung cancer progression, at least in part, by sponging miR-381-3p and inactivating the AKT/mTOR signaling pathway.

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