scholarly journals Effects of MicroRNA-195-5p on Biological Behaviors and Radiosensitivity of Lung Adenocarcinoma Cells via Targeting HOXA10

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Cheng Yuan ◽  
Rui Bai ◽  
Yanping Gao ◽  
Xueping Jiang ◽  
Shuying Li ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
G1 Phase ◽  
Potential Candidate ◽  
Antitumor Effects ◽  
Invasion And Migration ◽  
Phase Arrest ◽  
G1 Phase Arrest ◽  
And Migration

Objective. To explore the effects of miR-195-5p and its target gene HOXA10 on the biological behaviors and radiosensitivity of lung adenocarcinoma (LUAD) cells. Methods. The effects of miR-195-5p on LUAD cell proliferation, migration, invasion, cycle arrest, apoptosis, and radiosensitivity were investigated by in vitro experiments. The bioinformatics analysis was used to assess its clinical value and predict target genes. Double-luciferase experiments were used to verify whether the miR-195-5p directly targeted HOXA10. A xenograft tumor-bearing mouse model was used to examine its effects on the radiosensitivity of LUAD in vivo. Results. Both gain- and loss-of-function assays demonstrated that miR-195-5p inhibited LUAD cell proliferation, invasion, and migration, induced G1 phase arrest and apoptosis, and enhanced radiosensitivity. Double-luciferase experiments confirmed that miR-195-5p directly targeted HOXA10. Downregulation of HOXA10 also inhibited LUAD cell proliferation, migration, and invasion, induced G1 phase arrest and apoptosis, and enhanced radiosensitivity. The protein levels of β-catenin, c-myc, and Wnt1 were decreased by miR-195-5p and increased by its inhibitor. Moreover, the effects of the miR-195-5p inhibitor could be eliminated by HOXA10-siRNA. Furthermore, miR-195-5p improved radiosensitivity of LUAD cells in vivo. Conclusion. miR-195-5p has excellent antitumor effects via inhibiting cancer cell growth, invasion, and migration, arresting the cell cycle, promoting apoptosis, and sensitizing LUAD cells to X-ray irradiation by targeting HOXA10. Thus, miR-195-5p may serve as a potential candidate for the treatment of LUAD.

scholarly journals BRD4 inhibitor nitroxoline enhances the sensitivity of multiple myeloma cells to bortezomib in vitro and in vivo by promoting mitochondrial pathway-mediated cell apoptosis

2020 ◽  
Vol 11 ◽  
pp. 204062072093268
Author(s):  
Guang Li ◽  
Yan-Hua Zheng ◽  
Li Xu ◽  
Juan Feng ◽  
Hai-Long Tang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Tumor Model ◽  
G1 Phase ◽  
Bortezomib Treatment ◽  
Phase Arrest ◽  
G1 Phase Arrest

Background: Multiple myeloma (MM) is the second most common hematological neoplasm. Wide administration of bortezomib significantly improves the survival of MM patients compared with conventional chemotherapy. Bromodomain-containing protein 4 (BRD4) inhibitors also have been demonstrated to retard cell proliferation and induce cellular apoptosis in various cancers. However, it is unclear whether the BRD4 inhibitor nitroxoline plus bortezomib has a synergistic anti-tumor effect on MM. Methods: Cell viability was determined via 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle and cell apoptosis were assessed via flow cytometry. Protein expression levels were determined via western blotting. The expression of apoptosis-related proteins in xenograft tissue were detected by means of immunohistochemistry. Results: Treatment with nitroxoline or bortezomib suppressed cell proliferation, and caused G0/G1 phase arrest and apoptosis in H929 and RPMI8226 cells. Furthermore, nitroxoline intensified the retardation of cell proliferation, as well as further enhanced the G0/G1 phase arrest and apoptosis induced by bortezomib in H929 and RPMI8226 cells. The western blot analysis revealed that nitroxoline or bortezomib treatment markedly diminished the levels of Bcl-2 and cyclin D1, and increased the levels of p21, Bax, cleaved PARP and cleaved caspase-3. Combination of these two agents was observed to result in further marked changes on these levels compared with nitroxoline or bortezomib treatment alone. What is more, in the xenograft tumor model, combinative treatment markedly inhibited tumor growth compared with the single drug treatment. Conclusion: Combination of bortezomib with nitroxoline has a synergistic anti-tumor activity in MM cells and may be a novel treatment method for MM.

A VEGFR2 Antagonist Inhibits Cell Proliferation, Migration, and Invasion by Blocking the PI3K-Akt and MAPK Signaling Pathways in Thyroid Cancer

2021 ◽  
Author(s):  
Chunhao Liu ◽  
Zhao Liu ◽  
Hao Zhao ◽  
Yue Cao ◽  
Yansong Lin ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Thyroid Cancer ◽  
Cell Lines ◽  
Mapk Signaling ◽  
Vascular Endothelial ◽  
Antitumor Effects ◽  
Invasion And Migration ◽  
And Migration ◽  
Mapk Signaling Pathways

Abstract Background: Vascular endothelial growth factor receptor-2 (VEGFR2)-mediated signaling cascades are involved in proliferation, migration, survival, and permeability changes in vascular endothelial cells. It was thought that VEGFR2 antagonists exerted their antitumor effects by inhibiting angiogenesis in tumor tissues. However, some recent studies have found that they have significant direct antitumor effects in some tumors. The aim of this study was to explore the antitumor effects and mechanisms of VEGFR2 antagonists in thyroid cancer (TC).Methods: The antitumor efficacy of a VEGFR2 antagonist (apatinib) in TC cells was evaluated through a series of in vitro experiments, and xenograft models were used to test its in vivo antitumor activity. The antitumor mechanisms of the VEGFR2 antagonist were explored using western blotting and immunohistochemistry.Results: Compared with that in the normal human thyroid cell line HTori3, the expression of VEGFR2 in TC cell lines (including IHH4, BCPAP, TPC-1, C643, K1, and 8305C) was significantly increased, especially in the C643 and 8305C cell lines. VEGFR2 antagonist inhibited the proliferation of C643 and 8305C cells in a dose-dependent manner, significantly reduced the invasion and migration of these cells, induced G0/G1 phase arrest and promoted cancer cell apoptosis. Additionally, the antiproliferative effect of the VEGFR2 antagonist was significantly reduced after KDR gene knockdown. In vivo experiments showed that tumor growth in nude mice was significantly inhibited in response to apatinib. The western blot and immunohistochemistry results showed that the VEGFR2 antagonist significantly reduced the expression and phosphorylation of VEGFR2 and further inhibited the phosphorylation of the downstream molecules Akt and ERK1/2.Conclusions: The VEGFR2 antagonist inhibited cell proliferation, invasion and migration in TC by inhibiting the PI3K/Akt and MAPK signaling pathways and exerted direct antitumor effects. Thus, directly targeting VEGFR2 can be an effective strategy for TC expressing VEGFR2.

Knockdown CYP2S1 inhibits lung cancer cells proliferation and migration

2021 ◽  
pp. 1-9
Author(s):  
Huan Guo ◽  
Baozhen Zeng ◽  
Liqiong Wang ◽  
Chunlei Ge ◽  
Xianglin Zuo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Lung Cancer Cells ◽  
Invasion And Migration ◽  
And Migration

BACKGROUND: The incidence of lung cancer in Yunnan area ranks firstly in the world and underlying molecular mechanisms of lung cancer in Yunnan region are still unclear. We screened a novel potential oncogene CYP2S1 used mRNA microassay and bioinformation database. The function of CYP2S1 in lung cancer has not been reported. OBJECTIVE: To investigate the functions of CYP2S1 in lung cancer. METHODS: Immunohistochemistry and Real-time PCR were used to verify the expression of CYP2S1. Colony formation and Transwell assays were used to determine cell proliferation, invasion and migration. Xenograft assays were used to detected cell growth in vivo. RESULTS: CYP2S1 is significantly up-regulated in lung cancer tissues and cells. Knockdown CYP2S1 in lung cancer cells resulted in decrease cell proliferation, invasion and migration in vitro. Animal experiments showed downregulation of CYP2S1 inhibited lung cancer cell growth in vivo. GSEA analysis suggested that CYP2S1 played functions by regulating E2F targets and G2M checkpoint pathway which involved in cell cycle. Kaplan-Meier analysis indicated that patients with high CYP2S1 had markedly shorter event overall survival (OS) time. CONCLUSIONS: Our data demonstrate that CYP2S1 exerts tumor suppressor function in lung cancer. The high expression of CYP2S1 is an unfavorable prognostic marker for patient survival.

scholarly journals AC093797.1 as a Potential Biomarker to Indicate the Prognosis of Hepatocellular Carcinoma and Inhibits Cell Proliferation, Invasion, and Migration by Reprogramming Cell Metabolism and Extracellular Matrix Dynamics

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaoling Liu ◽  
Chenyu Wang ◽  
Qing Yang ◽  
Yue Yuan ◽  
Yunjian Sheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Overall Survival ◽  
Biological Function ◽  
Cell Metabolism ◽  
Hub Genes ◽  
Invasion And Migration ◽  
And Migration

Purpose: The risk signature composed of four lncRNA (AC093797.1, POLR2J4, AL121748.1, and AL162231.4.) can be used to predict the overall survival (OS) of patients with hepatocellular carcinoma (HCC). However, the clinical significance and biological function of AC093797.1 are still unexplored in HCC or other malignant tumors. In this study, we aimed to investigate the biological function of AC093797.1 in HCC and screen the candidate hub genes and pathways related to hepatocarcinogenesis.Methods: RT-qPCR was employed to detect AC093797.1 in HCC tissues and cell lines. The role of AC093797.1 in HCC was evaluated via the cell-counting kit-8, transwell, and wound healing assays. The effects of AC093797.1 on tumor growth in vivo were clarified by nude mice tumor formation experiments. Then, RNA-sequencing and bioinformatics analysis based on subcutaneous tumor tissue was performed to identify the hub genes and pathways associated with HCC.Results: The expression of AC093797.1 decreased in HCC tissues and cell lines, and patients with low expressed AC093797.1 had poor overall survival (OS). AC093797.1 overexpression impeded HCC cell proliferation, invasion, and migration in vitro and suppressed tumor growth in vivo. Compared with the control group, 710 differentially expressed genes (243 upregulated genes and 467 downregulated genes) were filtered via RNA-sequencing, which mainly enriched in amino acid metabolism, extracellular matrix structure constituents, cell adhesion molecules cams, signaling to Ras, and signaling to ERKs.Conclusion: AC093797.1 may inhibit cell proliferation, invasion, and migration in HCC by reprograming cell metabolism or regulating several pathways, suggesting that AC093797.1 might be a potential therapeutic and prognostic marker for HCC patients.

scholarly journals Cell Proliferation and Motility Are Inhibited by G1 Phase Arrest in 15-kDa Selenoprotein-Deficient Chang Liver Cells

2015 ◽  
Vol 38 (5) ◽  
pp. 457-465 ◽  
Author(s):  
Jeyoung Bang ◽  
Jang Hoe Huh ◽  
Ji-Woon Na ◽  
Qiao Lu ◽  
Bradley A. Carlson ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Liver Cells ◽  
G1 Phase ◽  
Phase Arrest ◽  
G1 Phase Arrest ◽  
Chang Liver

scholarly journals Promoter activation and following induction of the p21/WAF1 gene by flavone is involved in G1 phase arrest in A549 lung adenocarcinoma cells

FEBS Letters ◽  
1998 ◽  
Vol 437 (1-2) ◽  
pp. 61-64 ◽  
Author(s):  
Fulu Bai ◽  
Takayoshi Matsui ◽  
Naoko Ohtani-Fujita ◽  
Yoshizumi Matsukawa ◽  
Yi Ding ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
G1 Phase ◽  
Promoter Activation ◽  
Phase Arrest ◽  
Adenocarcinoma Cells ◽  
G1 Phase Arrest ◽  
Lung Adenocarcinoma Cells ◽  
P21 Waf1 ◽  
A549 Lung

scholarly journals The TWIST1-centered competing endogenous RNA network promotes proliferation, invasion, and migration of lung adenocarcinoma

Oncogenesis ◽  
2019 ◽  
Vol 8 (11) ◽  
Author(s):  
Wenjie Xia ◽  
Qixing Mao ◽  
Bing Chen ◽  
Lin Wang ◽  
Weidong Ma ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Messenger Rnas ◽  
Competing Endogenous Rna ◽  
Invasion And Migration ◽  
Non Coding Rnas ◽  
And Migration

Abstract The proposed competing endogenous RNA (ceRNA) mechanism suggested that diverse RNA species, including protein-coding messenger RNAs and non-coding RNAs such as long non-coding RNAs, pseudogenes and circular RNAs could communicate with each other by competing for binding to shared microRNAs. The ceRNA network (ceRNET) is involved in tumor progression and has become a hot research topic in recent years. To date, more attention has been paid to the role of non-coding RNAs in ceRNA crosstalk. However, coding transcripts are more abundant and powerful than non-coding RNAs and make up the majority of miRNA targets. In this study, we constructed a mRNA-mRNA related ceRNET of lung adenocarcinoma (LUAD) and identified the highlighted TWIST1-centered ceRNET, which recruits SLC12A5 and ZFHX4 as its ceRNAs. We found that TWIST1/SLC12A5/ZFHX4 are all upregulated in LUAD and are associated with poorer prognosis. SLC12A5 and ZFHX4 facilitated proliferation, migration, and invasion in vivo and in vitro, and their effects were reversed by miR-194–3p and miR-514a-3p, respectively. We further verified that SLC12A5 and ZFHX4 affected the function of TWIST1 by acting as ceRNAs. In summary, we constructed a mRNA-mRNA related ceRNET for LUAD and highlighted the well-known oncogene TWIST1. Then we verified that SLC12A5 and ZFHX4 exert their oncogenic function by regulating TWIST1 expression through a ceRNA mechanism.

Chemical Library Screening Identifies Novel Inhibitors of Cyclin D2 (CCND2) Transactivation That Selectively Induce Apoptosis in Multiple Myeloma Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3421-3421
Author(s):  
Rodger E. Tiedemann ◽  
Xinliang Mao ◽  
Chng-Xin Shi ◽  
Yuan Xiao Zhang ◽  
Stephen Palmer ◽  
...  
Keyword(s):  
Gentian Violet ◽  
Myeloma Cell ◽  
S Phase ◽  
G1 Phase ◽  
Cyclin D ◽  
Cyclin D2 ◽  
Myeloma Cells ◽  
Phase Arrest ◽  
G1 Phase Arrest

Abstract Multiple myeloma tumors universally target one of the three human cyclin D genes (CCND1, CCND2 or CCND3) for dysregulation (Bergsagel et al., 2005, Blood, 106:296). Using a lentivirus expressing CCND2 RNAi we first tested the effects of selective cyclin D2 knock down on My5 and H929 myeloma cell lines and found G0/G1 phase arrest, increased apoptosis and significant selective disadvantage in transfected cells. By comparison, knockout mouse models indicate that most somatic tissues can develop in the total absence of cyclin D1, D2 and D3 (Kozar et al., 2004, Cell,118:477). Targeted inhibition of specific cyclin D expression is therefore a rational therapeutic strategy in myeloma. To identify novel pharmaceutical inhibitors of CCND2 transactivation we developed an assay employing NIH 3T3 cells stably co-expressing the CCND2 transactivator c-Maf and the cyclin D2 promoter driving firefly luciferase (luc) and screened the Lopac (n=1280), Prestwick (n=1120) and Spectrum (n=2000) libraries of drugs and natural compounds. In a parallel MTS assay, the effect of each compound on 3T3 viability was determined, allowing exclusion of compounds that caused secondary suppression of CCND2 due to non-specific cytotoxicity. From the screen we identified 10 c-Maf independent putative CCND2 inhibitors. These included monensin, patulin, β-lapachone, camptothecin, dihydrogambogic acid, gentian violet, thapsigargin, brefeldin A, pristimerin and kinetin riboside. Three of the 10 compounds (gentian violet, thapsigargin and patulin) were not studied further due to toxicity cited in the literature. Subsequent validation studies using selected compounds in human myeloma cell lines (HMCL) confirmed successful suppression of both cyclin D2 and D1 proteins. Each of these compounds was then shown to be cytotoxic to a genetically diverse and standardized panel of 14 HMCL in MTT assays: monensin (10–760 nM), camptothecin (5–700nM), dihydrogambogic acid (250–800 nM), pristimerin (150–500 nM) and kinetin riboside (2.5–20μM). Cell cycle analysis confirmed induction of G0/G1 phase arrest for most compounds, consistent with cyclin D inhibition. However, camptothecin and b-lapachone induced S-phase arrest, suggesting secondary suppression of cyclin D by virtue of S-phase activity. Unsorted myeloma patient bone marrow samples demonstrated selective activity for pristimerin, dihydrogambogic acid and kinetin riboside against CD138+ myeloma cells compared with non malignant hematopoietic cells; by contrast monensin showed almost equal toxicity for normal cells. The triterpenoid, pristimerin, showed potent anti-myeloma activity and was examined in greater detail. Studies confirm that pristimerin rapidly inhibits cyclin D1, D2 and D3 expression (<6 hours) at nanomolar concentrations and induces apoptosis of primary myeloma cells characterized by caspase 9 cleavage and Annexin V binding. While pristimerin is cytotoxic to HMCL and patient myeloma cells at 0.1–0.15 mg/L, toxicity studies in vivo indicate that the drug is tolerated in mice at 2.5 mg/kg i.p. daily. In vivo activity against a xenograft model is currently being determined. Overall this targeted chemical biology screen has identified several compounds, including the triterpenoid, pristimerin, that are being further characterized for promising preclinical anti-myeloma activity.

scholarly journals SUN1 silencing inhibits cell growth through G0/G1 phase arrest in lung adenocarcinoma

2017 ◽  
Vol Volume 10 ◽  
pp. 2825-2833 ◽  
Author(s):  
Weiyi Huang ◽  
Haihua Huang ◽  
Lei Wang ◽  
Jiong Hu ◽  
Weifeng Song
Keyword(s):  
Cell Growth ◽  
Lung Adenocarcinoma ◽  
G1 Phase ◽  
Phase Arrest ◽  
G1 Phase Arrest

scholarly journals MiR-18a-5p Promotes NPC Cell Proliferation, Invasion, Migration, and EMT by Targeting SMAD2

2020 ◽  
Author(s):  
Pengcheng Li ◽  
Junhui Xing ◽  
Jianwu Jiang ◽  
Xinyu Tian ◽  
Xuemeng Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Invasion And Migration ◽  
Metastasis Model ◽  
And Migration ◽  
Dual Luciferase Reporter Assay

Abstract Background: Nasopharyngeal carcinoma (NPC) is the most common malignant tumor in the head and neck that is characterized by high local malignant invasion and distant metastasis. miR-18a-5p reportedly plays an important role in tumorigenesis and development. However, little is known about the mechanism underlying miR-18a-5p’s role in NPC.Methods：Quantitative real-time PCR was used to detect the expression of miR-18a-5p in NPC tissues and cell lines. MTT assay and plate clone formation assay were used to detect the effect of miR-18a-5p on NPC cell proliferation. Woundhealing assays and Transwell assays were used to detect the effect of miR-18a-5p on NPC cell invasion and migration. The expressions of epithelialmesenchymal transition (EMT)-related proteins N-cadherin, Vimentin, and E-cadherin were detected by Westernblot. Bioinformatics and dual-luciferase reporter assay were used to detect the targeting interaction between miR-18a-5p and SMAD2. Xenotransplantation and metastasis model were used to detect the effect of miR-18a-5p on NPC growth and metastasis in vivo.Results:miR-18a-5p was highly expressed in NPC tissues and cell lines. Overexpression of miR-18a-5p promotedNPC cell proliferation, invasion, migration, and EMT process, whereas inhibition of miR-18a-5p expression led to the oppositeresults. Results of dual-luciferase reporter assay showed that SMAD2 was the target gene of miR-18a-5p, and SMAD2 could reverse the effect of miR-18a-5p on NPC cell line. Xenotransplantation and metastasis model experiments in nude mice showed that miR-18a-5p promotesNPC growth and metastasis in vivo.Conclusions:Targeting SMAD2 downregulated miR-18a-5p expression, thereby promoting NPC cell proliferation, invasion, migration, and EMT.

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