scholarly journals LncRNA LINC00662 promotes colon cancer tumor growth and metastasis by competitively binding with miR-340-5p to regulate CLDN8/IL22 co-expression and activating ERK signaling pathway

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Bo Cheng ◽  
Aimei Rong ◽  
Quanbo Zhou ◽  
Wenlu Li
Keyword(s):  
Colon Cancer ◽  
Tumor Growth ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Target Genes ◽  
Erk Signaling ◽  
Biological Functions ◽  
Colon Cells ◽  
Invasion And Migration

Abstract Background LncRNA LINC00662 is closely related to the occurrence and development of cancer. This study aims to explore the effect of LINC00662 on colon cancer tumor growth and metastasis and its molecular mechanism. Methods CCK8, colony formation, transwell, scratch wound, TUNEL, flow cytometry, RT-PCR, western blotting and immunohistochemistry assays were used to detect the proliferation, apoptosis, invasion and migration of colon cancer cell and mRNA and protein expressions. Luciferase reporter and RNA pull down assays were used to detect the combination of LINC00662 and miR-340-5p or IL22 and the combination of miR-340-5p and CLDN8/IL22. Co-immunoprecipitation were used to detect the co-expression of CLDN8 and IL22 in colon cell lines. The targets of LINC00662 were predicated by Starbase v2.0. The target genes of miR-340-5p were predicated by miRDB and TargetScan. GO and KEGG enrichment analysis were performed by DAVID website. Results LINC00662 was up-regulation in colon cancer tissues and cell lines. Univariate Cox regression analysis showed that the LINC00662 expression level was related to the poor prognosis. LINC00662-WT and miR-340-5p mimics co-transfection depressed luciferase activity and IL22/CLDN8-WT and miR-340-5p inhibitors co-transfection memorably motivated luciferase activity. LINC00662 overexpression promoted cell proliferation, invasion and migration, and inhibited cell apoptosis in colon cancer. In vivo xenograft studies in nude mice manifested that LINC00662 overexpression prominently accelerate tumor growth. There was an opposite reaction in the biological functions of colon cells and tumor growth between LINC00662 overexpression and LINC00662 inhibition in vitro and in vivo. The functions of miR-340-5p mimics regulating the biological functions of colon cells and tumor growth were consistent with those of LINC00662 inhibition. CLDN8 and IL22, as target genes of miR-340-5p, reversed the functions of LINC00662 affecting the biological functions of colon cells and the protein levels of Bax, Bcl-2, XIAP, VEGF, MMP-2, E-cadherin and N-cadherin. Co-immunoprecipitation experiments indicated that CLDN8 directly interact with IL22 in colon cell lines. LINC00662 regulated CLDN8 and IL22 expressions and the activation of ERK signaling pathway via targeting miR-340-5p. Conclusion LINC00662 overexpression promoted the occurrence and development of colon cancer by competitively binding with miR-340-5p to regulate CLDN8/IL22 co-expression and activating ERK signaling pathway.

HOXA3 promotes tumor growth of human colon cancer through activating EGFR/Ras/Raf/MEK/ERK signaling pathway

2017 ◽  
Vol 119 (3) ◽  
pp. 2864-2874 ◽  
Author(s):  
Xianxiang Zhang ◽  
Guangwei Liu ◽  
Lei Ding ◽  
Tao Jiang ◽  
Shihong Shao ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Tumor Growth ◽  
Signaling Pathway ◽  
Human Colon ◽  
Erk Signaling ◽  
Human Colon Cancer

scholarly journals Overexpression of protein regulator of cytokinesis 1 facilitates tumor growth and indicates unfavorable prognosis of patients with colon cancer

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Tianxiang Xu ◽  
Xiaoxia Wang ◽  
Xiangdong Jia ◽  
Weishi Gao ◽  
Junhua Li ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cell Lines ◽  
Clinicopathological Characteristics ◽  
Tumor Formation ◽  
Down Regulation ◽  
Cancer Tissues

Abstract Background Protein regulator of cytokinesis 1 (PRC1) has been reported to play important role in the pathogenesis of various cancers. However, its role in colon cancer has not been studied. Here, we aimed to investigate the biological functions and potential mechanism of PRC1 in colon cancer. Methods The expression level of PRC1 in colon cancer tissues and cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemical (IHC) staining of a tissue microarray (TMA). Furthermore, colon cancer cell lines HCT116 and SW480 were treated with short hairpin RNAs against PRC1. The biological function of PRC1 was determined by MTT proliferation, colony formation assay, cell cycle, and apoptosis assays. Then, an in vivo tumor formation assay was conducted to explore the effects of PRC1 on tumor growth. Results The mRNA and protein expression levels of PRC1 were highly expressed in colon cancer tissues and cell lines. PRC1 expression was associated with clinicopathological characteristics and overall survival of patients with colon cancer. Knockdown of PRC1 could decrease proliferation and colony forming ability of colon cancer cells, as well as arrested more cells at G2/M phase and promoted cell apoptosis. In cancer cells, the expression pattern of protein regulators included in cell cycle and apoptosis progress were reverted by PRC1 down-regulation. Additionally, PRC1 down-regulation could suppress colon tumor growth and differentiation. Conclusions We confirmed that PRC1 was overexpressed in colon cancer and was associated with poor prognosis of colon cancer patients. PRC1 down-regulation could arrest cell cycle at G2/M stage, inhibit proliferation, and elicit apoptosis. These findings showed the potential of PRC1 to be used for therapeutic approaches in colon cancer.

scholarly journals SIRT2 mediated down regulation of FOXM1 in response to TGFβ through the RAF-MEK-ERK signaling pathway in colon cancer

2021 ◽  
pp. 20-20
Author(s):  
Ozkan Ozden ◽  
Seong-Hoon Park
Keyword(s):  
Colon Cancer ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Cancer Cell ◽  
Transforming Growth Factor ◽  
Cancer Cell Lines ◽  
Colon Cancer Cell ◽  
Erk Signaling ◽  
Embryonic Fibroblasts ◽  
Colon Cancer Cell Lines

The transcription factor forkhead box M1 (FOXM1) is frequently upregulated in many solid tumors, including those in the colon. As a master regulator, the sirtuin (SIRT) protein family is comprised of seven nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases/adenosine diphosphate (ADP) ribosyl transferases whose activities are associated with aging and cancer. In this study, we determined whether a cytoplasmic member of SIRTs, SIRT2, influences the expression of oncogenic FOXM1 in colon cancer in vitro. The association of SIRT2 and FOXM1 were analyzed using SIRT2 knockout mouse embryonic fibroblasts and SIRT2 knocked-down and overexpressing HCT116 colon cancer cell lines. Cell lines were treated with 10 ng/mL transforming growth factor-beta (TGF?) for 24 h. SIRT2 could downregulate FOXM1 through the TGF? mitogen-activated protein kinase (RAFMEK- ERK) signaling pathway in genetically alteredmouse embryonic fibroblasts and colon cancer cell lines. The indirect association between SIRT2 and FOXM1 through TGF? may be important because activators or inhibitors of SIRT2 could provide a potential approach to downregulate FOXM1 in gastrointestinal cancers.

scholarly journals LINC00346 Sponges miR-30c-2-3p to Promote the Development of Lung Adenocarcinoma by Targeting MYBL2 and Regulating CELL CYCLE Signaling Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Qian Xu ◽  
Zhenwu Xu ◽  
Kai Zhu ◽  
Jinlan Lin ◽  
Bo Ye
Keyword(s):  
Cell Cycle ◽  
Tumor Growth ◽  
Lung Adenocarcinoma ◽  
Signaling Pathway ◽  
Cell Cycle Progression ◽  
Target Genes ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Cell Cycle Signaling

BackgroundLINC00346 has recently been reported to regulate the development of several cancer types, but its biological functions and underlying mechanisms in lung adenocarcinoma (LUAD) have not been elucidated. The purpose of this study was to investigate the molecular mechanism of LINC00346 in the progression of LUAD.MethodsBioinformatics was performed to find the target lncRNA, miRNA and mRNA, and the binding relationship between the target genes was verified by dual luciferase reporter gene and RIP assays. Fluorescence in situ hybridization was used to detect the location of LINC00346 in LUAD tissues. The expressions of LINC00346, miR-30c-2-3p and MYBL2 in each group were detected by qRT-PCR, and western blot was performed to detect expressions of MYBL2 and CELL CYCLE related proteins. Proliferation, metastasis, apoptosis and cell cycle of LUAD cells were detected by CCK-8, colony formation, Transwell and flow cytometry assays, respectively. Mouse xenograft models were established to further determine the effects of LINC00346 on LUAD tumor growth in vivo.ResultsLINC00346 was upregulated in LUAD tissues and cells and was mainly localized in the cytoplasm. Knockdown of LINC00346 inhibited tumor growth in vivo, proliferation, metastasis and cell cycle progression, while induced apoptosis. LINC00346 sponged miR-30c-2-3 by targeting MYBL2 and regulating CELL CYCLE signaling pathway. Inhibiting miR-30c-2-3p or overexpressing MYBL2 could reverse the inhibitory effect of LINC00346 knockdown on LUAD process.ConclusionsLINC00346 as a ceRNA played a carcinogenic role in the development of LUAD via miR-30c-2-3p/MYBL2 axis regulating the CELL CYCLE signaling pathway. The study generally elucidated the mechanism by which LINC00346 regulated the development of LUAD, providing new ideas for the diagnosis and treatment of LUAD guided by lncRNA.

scholarly journals Overexpression of Agrin promotes tumor proliferation and correlates with poor prognosis in cholangiocarcinoma

2020 ◽  
Author(s):  
Meimei He ◽  
Shasha Ji ◽  
Junxue Tu ◽  
Dan Lou
Keyword(s):  
Cell Cycle ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Target Genes ◽  
Intrahepatic Metastasis ◽  
Control Group ◽  
Hippo Signaling ◽  
Tumor Characteristics ◽  
Hippo Signaling Pathway

Abstract Background Agrin exists as a shorter Type II Transmembrane form with an internal signal peptide, and is closely correlated with the activation of multiple intercellular signaling pathways. The aim of the present study was to investigate the role of Agrin in the development of cholangiocarcinoma (CCA). Methods RT-qPCR and western blotting were performed to detect the expressional level of target genes, including Agrin, in CCA tissues or cell lines. The correlation between Agrin, and tumor characteristics and prognosis, was analyzed using independent sample t-test, the Kaplan-Meier method and Cox proportional hazard model, respectively. Proliferation, migration, invasion and tumorigenesis in CCA cells was determined by CCK8 assay, cell cycle detection, Transwell assay and nude mouse tumorigenicity assay, respectively. Results Agrin was significantly upregulated in CCA tissues, as compared to the adjacent non-tumor tissues, and was correlated with poorer tumor characteristics such as portal vein tumor thrombus, intrahepatic metastasis and poor survival. The Agrin overexpression in CCA cell lines clearly promoted proliferation, colony formation, migration, invasion and cell cycle progression, but Agrin knockdown had the opposite effect. Furthermore, CCA cells with inhibitory Agrin expression presented with less and smaller tumors, as compared with the control group in vivo. Mechanistic analysis indicated that Agrin was able to activate the Hippo signaling pathway and induce yap to enter the cell nucleus. Conclusions We found that Agrin promotes the CCA progression via activating the Hippo signaling pathway, which could be a potentially promising target for CCA treatment.

Preclinical study of MEK1/2 inhibitor AZD6244 combined with gemcitabine for treatment of biliary cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 240-240
Author(s):  
Junyao Xu ◽  
Jennifer J. Knox ◽  
Ming Sound Tsao ◽  
Eric Xueyu Chen ◽  
Pinjiang Cao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Preclinical Study ◽  
Erk Signaling ◽  
Therapeutic Effects ◽  
Biliary Cancer

240 Background: MEK1/2 is an integral component of the Ras/Raf/MEK/ERK signaling pathway, implicated in uncontrolled cell proliferation and cell survival, a key hallmark of cancer. AZD6244, a novel inhibitor of MEK1/2, is currently completing Phase II clinical trials in biliary cancer, with modest antitumor activity observed as monotherapy. Gemcitabine is a cytotoxic drug commonly used in biliary cancer therapy but many patients showed early resistance. In this preclinical study, we investigated the sequence-dependent antitumor effects of AZD6244 combined with gemcitabine in biliary cancer models. Methods: Two biliary cancer cell lines (EGI-1 and TFK-1) were used. In vitro the effects of single drug or three combination protocols(concurrently; AZD6244 followed by GEM or Gem followed by AZD6244) on cell proliferation, DNA synthesis, and cell cycle distribution were evaluated by MTS, clonogenic assay, EdU uptake and flow cytometry. Drug interactions were analyzed by Chou-Talaly method. In vivo, 4 tumor models subcutaneously xenografted in SCID mice from the two cell lines and 2 human patients were set up to compare the therapeutic effects of different sequence-scheduled combinations. Results: AZD6244 caused G1-S cell cycle arrest in biliary cancer cells in vitro and in vivo, and this effect is correlated with the MEK/ERK signaling pathway blocking. Synchronized progression of the population through S phase were observed in 15h after removal of AZD6244 in cell culture or 48h after final dose of acute AZD6244 treatment in vivo. Antagonistic or additive effects was observed in vitro when combination were given as concurrently(CI=2.03~2.46) or Gem followed by AZD6244(CI=1.34~1.78). In contrast, a synergistic antiproliferative activity was obtained when AZD6244 was given first followed by a drug-free interval before Gem treatment (CI=0.53~0.69). In vivo, the best therapeutic effects were obtained with the sequence of AZD6244 followed by Gem, compared with concurrent or reverse sequence. Conclusions: This study provides a sound rationale for a Phase II trial of a potentially synergistic sequence of MEK inhibitor AZD6244 followed by gemcitabine in patients with advanced biliary cancer.

Cinobufacini Inhibits Colon Cancer Invasion and Metastasis via Suppressing Wnt/β-Catenin Signaling Pathway and EMT

2020 ◽  
Vol 48 (03) ◽  
pp. 703-718 ◽  
Author(s):  
Jie Wang ◽  
Han Cai ◽  
Qiaoli Liu ◽  
Yue Xia ◽  
LiKai Xing ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Signaling Pathway ◽  
Cancer Invasion ◽  
In Vivo Studies ◽  
Colon Cancer Cells ◽  
Invasion And Metastasis ◽  
Invasion And Migration ◽  
And Migration

Cinobufacini is a well-known Chinese medicine extracted from Venenum Bufonis, also called Chan Su. It has been used clinically for various cancers, including colon cancer. However, the function of Cinobufacini on colon cancer invasion and metastasis, and its underlying molecular mechanism, is still not clear. In this study, we investigated the function and mechanism of Cinobufacini on colon cancer invasion and metastasis both in vitro and in vivo studies. Human colon cancer cells were cultured. CCK assay was used to detect the effect of Cinobufacini on colon cancer cells proliferation. The invasion and migration abilities were observed by transwell assays, and the expression of invasion and migration related genes MMP2, MMP9, and epithelial-to-mesenchymal transition (EMT) relate genes were observed by Western blot assays. An orthotopic xenograft model in nude mice was established using colon cancer HCT116 cells, and the function of Cinobufacini on colon cancer invasion and metastasis were observed in vivo. We found Cinobufacini significantly inhibited colon cancer cell proliferation in a dose/time-dependent manner; the invasion and migration abilities of colon cancer were decreased after treated with Cinobufacini. The metastasis and EMT related genes MMP9, MMP2, N-cadherin and Snail were obviously down-regulated, while the expression of E-cadherin was up-regulated after treatment with Cinobufacini. The Wnt/[Formula: see text]-catenin signaling pathway related genes were observed using WB,and results show that the expression of [Formula: see text]-catenin, wnt3a, c-myc, cyclin D1, and MMP7 were all down-regulated after being treated with cinobufacini, while the expression of APC was up-regulated. In vivo studies of the volume and weight of orthotopic xenograft tumors showed significantly shrinkage in the Cinobufacini group compared to the control group. The enterocoelia and liver metastasis tumors were significantly decreased, and the expression of MMP9, MMP2, and [Formula: see text]-catenin were also down-regulated, while E-cadherin was up-regulated in vivo after the treatment with Cinobufacini. Our data proves that Cinobufacini can inhibit colon cancer invasion and metastasis both in vitro and in vivo; the mechanism is related by suppressing the Wnt/[Formula: see text]-catenin signaling pathway and then inhibiting the EMT of CRC.

scholarly journals Erratum

2021 ◽  
Vol 28 (6) ◽  
pp. 681-682
Author(s):  
Juan Gu ◽  
Chang-fu Cui ◽  
Li Yang ◽  
Ling Wang ◽  
Xue-hua Jiang
Keyword(s):  
Signaling Pathway ◽  
Target Genes ◽  
Mrna Level ◽  
Xenograft Model ◽  
Dependent Manner ◽  
Invasion And Migration ◽  
Downstream Target ◽  
And Migration

Colon cancer (CC) is the third most common cancer worldwide. Emodin is an anthraquinone-active substance that has the ability to affect tumor progression. Our study aims to explore the effects and the relevant mechanism of emodin on the invasion and migration of CC in vitro and in vivo. In our study, we found that emodin inhibited the invasion and migration abilities of RKO cells and decreased the expression of matrix metalloproteinase-7 (MMP-7), MMP-9, and vascular endothelial growth factor (VEGF) in a dose-dependent manner. Further research suggested that emodin inhibited EMT by increasing the mRNA level of E-cadherin and decreasing the expression of N-cadherin, Snail, and -catenin. Emodin also significantly inhibited the activation of the Wnt/-catenin signaling pathway by downregulating the expression of related downstream target genes, including TCF4, cyclin D1, and c-Myc. A Wnt/-catenin signaling pathway agonist abolished the effect of emodin on EMT and cell mobility, suggesting that emodin exerted its regulating role through the Wnt/-catenin pathway. The CC xenograft model was established to study the antitumor efficiency of emodin in vivo. The in vivo study further demonstrated that emodin (40 mg/kg) suppressed tumor growth by inhibiting EMT via the Wnt/-catenin signaling pathway in vivo. Taken together, we suggest that emodin inhibits the invasion and migration of CC cells in vitro and in vivo by blocking EMT, which is related with the inhibition of the Wnt/-catenin signaling pathway.

scholarly journals OXCT1 Enhances Gemcitabine Resistance Through NF-κB Pathway in Pancreatic Ductal Adenocarcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Jinsheng Ding ◽  
Hui Li ◽  
Yang Liu ◽  
Yongjie Xie ◽  
Jie Yu ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Bioinformatics Analysis ◽  
Gene Set Enrichment Analysis ◽  
Ductal Adenocarcinoma ◽  
Pdac Cell ◽  
Coa Transferase

BackgroundPancreatic ductal adenocarcinoma (PDAC) is a type of malignant tumor with a five-year survival rate of less than 10%. Gemcitabine (GEM) is the most commonly used drug for PDAC chemotherapy. However, a vast majority of patients with PDAC develop resistance after GEM treatment.MethodsWe screened for GEM resistance genes through bioinformatics analysis. We used immunohistochemistry to analyze 3-oxoacid CoA-transferase 1 (OXCT1) expression in PDAC tissues. The survival data were analyzed using the Kaplan–Meier curve. The expression levels of the genes related to OXCT1 and the NF-κB signaling pathway were quantified using real−time quantitative PCR and western blot analyses. We performed flow cytometry to detect the apoptosis rate. Colony formation assay was performed to measure the cell proliferation levels. The cytotoxicity assays of cells were conducted using RTCA. The downstream pathway of OXCT1 was identified via the Gene Set Enrichment Analysis. Tumor growth response to GEM in vivo was also determined in mouse models.ResultsBioinformatics analysis revealed that OXCT1 is the key gene leading to GEM resistance. Patients with high OXCT1 expression exhibited short relapse-free survival under GEM treatment. OXCT1 overexpression in PDAC cell lines exerted inhibitory effect on apoptosis after GEM treatment. However, the down-regulation of OXCT1 showed the opposite effect. Blocking the NF-κB signaling pathway also reduced GEM resistance of PDAC cells. Tumor growth inhibition induced by GEM in vivo reduced after OXCT1 overexpression. Moreover, the effect of OXCT1 on GEM refractoriness in PDAC cell lines was reversed through using an NF-κB inhibitor.ConclusionOXCT1 promoted GEM resistance in PDAC via the NF-κB signaling pathway both in vivo and in vitro. Our results suggest that OXCT1 could be used as a potential therapeutic target for patients with PDAC.

Amentoflavone Effectively Blocked the Tumor Progression of Glioblastoma via Suppression of ERK/NF-κB Signaling Pathway

2019 ◽  
Vol 47 (04) ◽  
pp. 913-931 ◽  
Author(s):  
Fei-Ting Hsu ◽  
I-Tsang Chiang ◽  
Yu-Cheng Kuo ◽  
Te-Chun Hsia ◽  
Chin-Chung Lin ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Signaling Pathway ◽  
Unmet Need ◽  
In Vivo Studies ◽  
Tumor Growth Inhibition ◽  
Beneficial Result ◽  
Invasion And Migration ◽  
And Migration

Glioblastoma is the most common primary malignant tumor of the central nervous system, with an annual incidence of 5.26 per 100000 people. The clinical outcome of standard therapy and the survival rate remain poor; therefore, there is an unmet need for a new strategy to treat this lethal disease. Although amentoflavone was known to have anticancer potential in various types of cancers, its antiglioblastoma ability and mechanism remain unrecognized. We demonstrated that amentoflavone may suppress glioblastoma invasion and migration by transwell assay. Moreover, we established NF-[Formula: see text]B reporter gene system and used that for verifying NF-[Formula: see text]B inhibition efficacy of amentoflavone on in vitro and in vivo studies. Here, we indicated that amentoflavone not only diminished NF-[Formula: see text]B activation, but also reduced NF-[Formula: see text]B-mediated downstream oncogenes expression, such as MMP-2, MMP-9, XIAP, cyclinD1 and VEGF, which was elucidated by Western blot and immunohistochemistry (IHC). Tumor growth inhibition and NF-[Formula: see text]B reduction was found in the amentoflavone treatment group, which was revealed by the glioblastoma-bearing animal model. In this study, we also used ERK inhibitor and NF-[Formula: see text]B inhibitor (QNZ) to confirm whether the beneficial result of amentoflavone on glioblastoma was mainly regulated by blockage of ERK/NF-[Formula: see text]B signaling. In summary, ERK/NF-[Formula: see text]B signaling pathway has a role in the inhibition of tumor growth by amentoflavone in glioblastoma.

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