共查询到20条相似文献,搜索用时 15 毫秒
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Jingde Chen Li Li Zhuqing Zhou Shijun Yu Yandong Li Yong Gao 《Experimental cell research》2019,374(1):12-18
Human phosphatidylinositol-4-phosphate adaptor protein-2 (FAPP2) is well-known to function as a cytoplasmic lipid transfer protein during vesicle maturation. However, the expression and role of FAPP2 in tumor remain elusive. In this study, data from immunohistochemical assays displayed that FAPP2 was remarkably upregulated (57.8%) in 90 cases of colon cancer samples in contrast to their corresponding adjacent tissues. Disruption of FAPP2 by CRISPR/Cas9 technique in colon cancer cells led to an attenuated effect on cell growth analyzed by CCK8 and colony formation assays. Meanwhile, the tumorigenicity of FAPP2 downregulated cells also decreased in nude mice model. Accordantly, CCK8 assays also indicated that FAPP2 overexpression could promote colon cancer cell growth. In addition, dual luciferase reporter assays and western blot analyses revealed that Wnt/β-catenin signaling was involved in the FAPP2-regulated tumor cell growth. These findings suggest that FAPP2 could act as an oncogene in the regulation of tumor growth and may provide a new therapeutic target for human colon cancer. 相似文献
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Wenji Yan Kongming Wu James G Herman Malcolm V Brock Fran?ois Fuks Lili Yang Hongbin Zhu Yazhuo Li Yunsheng Yang Mingzhou Guo 《Epigenetics》2013,8(12):1373-1383
Colorectal cancer (CRC) is one of the common malignant tumors worldwide. Both genetic and epigenetic changes are regarded as important factors of colorectal carcinogenesis. Loss of DACH1 expression was found in breast, prostate, and endometrial cancer. To analyze the regulation and function of DACH1 in CRC, 5 colorectal cancer cell lines, 8 cases of normal mucosa, 15 cases of polyps and 100 cases of primary CRC were employed in this study. In CRC cell lines, loss of DACH1 expression was correlated with promoter region hypermethylation, and re-expression of DACH1 was induced by 5-Aza-2'-deoxyazacytidine treatment. We found that DACH1 was frequently methylated in primary CRC and this methylation was associated with reduction in DACH1 expression. These results suggest that DACH1 expression is regulated by promoter region hypermethylation in CRC. DACH1 methylation was associated with late tumor stage, poor differentiation, and lymph node metastasis. Re-expression of DACH1 reduced TCF/LEF luciferase reporter activity and inhibited the expression of Wnt signaling downstream targets (c-Myc and cyclinD1). In xenografts of HCT116 cells in which DACH1 was re-expressed, tumor size was smaller than in controls. In addition, restoration of DACH1 expression induced G2/M phase arrest and sensitized HCT116 cells to docetaxel. DACH1 suppresses CRC growth by inhibiting Wnt signaling both in vitro and in vivo. Silencing of DACH1 expression caused resistance of CRC cells to docetaxel. In conclusion, DACH1 is frequently methylated in human CRC and methylation of DACH1 may serve as detective and prognostic marker in CRC. 相似文献
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MicroRNA‐1271 suppresses the proliferation and invasion of colorectal cancer cells by regulating metadherin/Wnt signaling 下载免费PDF全文
Xiaoli Sun Hongjun Zhai Xi Chen Ranran Kong Xinwu Zhang 《Journal of biochemical and molecular toxicology》2018,32(2)
Recent studies have reported an important role for microRNA‐1271 (miR‐1271) in tumorigenesis. However, the role of miR‐1271 in colorectal cancer remains unknown. Here, we found that miR‐1271 was significantly decreased in colorectal cancer tissues and cell lines. Overexpression of miR‐1271 inhibited cell proliferation, colony formation, cell invasion, and induced cell cycle arrest in colorectal cancer cells. Metadherin (MTDH) was identified as a target gene of miR‐1271. Moreover, miR‐1271 negatively regulated MTDH expression in colorectal cancer cells and reversely correlated with MTDH expression in colorectal cancer specimens. Additionally, miR‐1271 also regulated the activation of Wnt signaling in colorectal cancer cells. The restoration of MTDH expression significantly reversed the antitumor effect of miR‐1271 in colorectal cancer cells. These findings indicate an important role for miR‐1271/MTDH in the tumorigenesis of colorectal cancer, and suggest that miR‐1271 may be a novel therapeutic target for colorectal cancer. 相似文献
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Pathirennehelage Chandrasekera Mark Perfetto Congyu Lu Minghui Zhuo Harinath Bahudhanapati Jiejing Li Wei-Chih Chen Pallavi Kulkarni Laura Christian Jun Liu Yvette Y. Yien Chundong Yu Shuo Wei 《The Journal of biological chemistry》2022,298(8)
Ephrin-B signaling has been implicated in many normal and pathological processes, including neural crest development and tumor metastasis. We showed previously that proteolysis of ephrin-B ligands by the disintegrin metalloprotease ADAM13 is necessary for canonical Wnt signal activation and neural crest induction in Xenopus, but it was unclear if these mechanisms are conserved in mammals. Here, we report that mammalian ADAM9 cleaves ephrin-B1 and ephrin-B2 and can substitute for Xenopus ADAM13 to induce the neural crest. We found that ADAM9 expression is elevated in human colorectal cancer (CRC) tissues and that knockdown (KD) of ADAM9 inhibits the migration and invasion of SW620 and HCT116 CRC cells by reducing the activity of Akt kinase, which is antagonized by ephrin-Bs. Akt is a signaling node that activates multiple downstream pathways, including the Wnt and mTOR pathways, both of which can promote CRC cell migration/invasion. Surprisingly, we also found that KD of ADAM9 downregulates Wnt signaling but has negligible effects on mTOR signaling in SW620 cells; in contrast, mTOR activity is suppressed while Wnt signaling remains unaffected by ADAM9 KD in HCT116 cells. These results suggest that mammalian ADAM9 cleaves ephrin-Bs to derepress Akt and promote CRC migration and invasion; however, the signaling pathways downstream of Akt are differentially regulated by ADAM9 in different CRC cell lines, reflecting the heterogeneity of CRC cells in responding to manipulations of upstream Akt regulators. 相似文献
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Y Dai G Wilson B Huang M Peng G Teng D Zhang R Zhang M P A Ebert J Chen B C Y Wong K W Chan J George L Qiao 《Cell death & disease》2014,5(4):e1170
Dysregulated Notch signaling has a critical role in the tumorigenesis. Jagged1, a Notch ligand, is overexpressed in various human cancers. Recent studies revealed the involvement of Jagged1 in colorectal cancer (CRC) development. These basic studies provide a promising potential for inhibition of the Notch pathway for the treatment of CRC. Herein, we aimed to investigate the consequences of targeting Jagged1 using shRNA on CRC both in vitro and in vivo to test their potential to inhibit this key element for CRC treatment. We found that downregulation of Jagged1 with lentiviral Jagged1-shRNA resulted in decreased colon cancer cell viability in vitro, most likely mediated through reduced cell proliferation. Importantly, Jagged1 knockdown induced G0/G1 phase cell cycle arrest, with reduced Cyclin D1, Cyclin E and c-Myc expression. Silencing of Jagged1 reduced the migration and invasive capacity of the colon cancer cells in vitro. Furthermore, colon cancer cells with knockdown of Jagged1 had much slower growth rate than control cells in a xenograft mouse model in vivo, with a marked downregulation of cell proliferation markers (PCNA, Ki-67, and c-Myc) and metastasis markers (MMP-2 and MMP-9). These findings rationalize a mechanistic approach to CRC treatment based on Jagged1-targeted therapeutic development. 相似文献
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Yuxi Tian Liangfang Shen Fujun Li Junwen Yang Xiaoping Wan Miao Ouyang 《Journal of cellular physiology》2020,235(1):442-453
Colorectal cancer (CRC) is commonly known as one of the most prominent reasons for cancer-related death in China. Ras homolog enriched in brain (RHEB) and the mammalian target activity of rapamycin (mTOR) signaling pathway were found correlated with CRC, but their specific interaction in CRC was still to be investigated. Therefore, we explored whether RHEB gene silencing affected the cell proliferation, differentiation, and apoptosis by directly targeting the mTOR signaling pathway in cells previously harvested from CRC patients. A microarray analysis was subsequently conducted to investigate the relationship between RHEB and mTOR. Eighty-three adjacent normal tissues and CRC tissues were selected. Immunohistochemistry was carried out to detect the positive expression rates of RHEB and Ki-67 in the CRC tissues. Cells were then transfected with different siRNAs to investigate the potential effects RHEB would have on CRC progression. The expressions of RHEB, 4EBP1, ribosomal protein S6 kinase (p70S6K), proliferating cell nuclear antigen (PCNA), B cell lymphoma 2 (bcl-2), and bcl-2-associated X protein (bax) were determined and then the cell cycle, cell proliferation, and apoptotic rate were also measured. We identified RHEB and mTOR as upregulated genes in CRC. Cells treated with RHEB silencing showed a decreased extent of mTOR, p70S6K, 4EBP1 phosphorylation and expression of RHEB, Ki-67, mTOR, p70S6K, 4EBP1, bcl-2, and PCNA as well as decreased activity of cell proliferation and differentiation; although, the expression of bax was evidently higher. Collectively, our data propose the idea that RHEB gene silencing might repress cell proliferation and differentiation while accelerating apoptosis via inactivating the mTOR signaling pathway. 相似文献
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Zhang K Ye C Zhou Q Zheng R Lv X Chen Y Hu Z Guo H Zhang Z Wang Y Tan R Liu Y 《Cell biochemistry and function》2007,25(6):767-774
The approximately 14 kb mRNA of the polycystic kidney disease gene PKD1 encodes a large ( approximately 460 kDa) protein, termed polycystin-1 (PC-1), that is responsible for autosomal dominant polycystic kidney disease (ADPKD). The unique organization of its multiple adhesive domains (16 Ig-like domains/PKD domains) suggests that it may play an important role in cell-cell/cell-matrix interactions. Here we demonstrated that PKD1 promoted cell-cell and cell-matrix interactions in cancer cells, indicating that PC-1 is involved in the cell adhesion process. Furthermore in this study, we showed that PKD1 inhibited cancer cells migration and invasion. And we also showed that PC-1 regulated these processes in a process that may be at least partially through the Wnt pathway. Collectively, our data suggest that PKD1 may act as a novel member of the tumor suppressor family of genes. 相似文献
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Mehran Pashirzad Mojtaba Shafiee Majid Khazaei Hamid Fiuji Mikhail Ryzhikov Saman Soleimanpour AmirReza Hesari Amir Avan Seyed Mahdi Hassanian 《Journal of cellular physiology》2019,234(2):1237-1247
Prostate cancer is a major cause of cancer-related death in males. Wnt/β-catenin signaling plays a critical role in the pathogenesis of this disease by regulating angiogenesis, drug resistance, cell proliferation, and apoptosis. Suppression of Wnt canonical or noncanonical signaling pathways via Wnt biological or pharmacological antagonists is a potentially novel therapeutic approach for patients with prostate cancer. This review summarizes the role of Wnt signaling inhibitors in the pathogenesis of prostate cancer for a better understanding and hence a better management of this disease. 相似文献
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Yang Yang Yanan Zhao Nanjun Hu Jia Zhao Yuansong Bai 《Cell biology international》2019,43(12):1463-1470
Colorectal cancer (CRC) is the third most common cancer in all races worldwide in recent years. The survival of the CRC patients is mostly affected by the stage of the disease at the time of diagnosis. Thus, the current challenge is to find sensitive and reliable biomarkers in early screening of CRC. Recently, emerging evidence has shown that long non‐coding RNAs (lncRNAs) may play crucial roles in tumorigenesis. In this study, we found that lncRNA KIAA0125 was downregulated in colorectal tissues and cells. The functional study demonstrated that overexpression of KIAA0125 suppressed cell proliferation, migration, and invasion whereas the reversal effects were seen in silencing experiment. Besides, KIAA0125 inhibited epithelial–mesenchymal transition through Wnt/β‐catenin signaling in CRC. Our findings suggested that KIAA0125 may act as an oncosupressor gene and could be considered as a potential diagnosis biomarker in CRC. 相似文献
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Isabelle Ariane Bley Anabel Zwick Muriel Charlotte Hans Katrin Thieser Viktoria Wagner Nicole Ludwig Oybek Khalmurzaev Vsevolod Borisovich Matveev Philine Loertzer Alexey Pryalukhin Arndt Hartmann Carol-Immanuel Geppert Hagen Loertzer Heiko Wunderlich Carsten Maik Naumann Holger Kalthoff Kerstin Junker Sigrun Smola Stefan Lohse 《Translational oncology》2022,15(1)
Penile squamous cell cancer (PSCC) is the most frequent penile malignant disease. Infections with human papillomaviruses (HPV) are a major etiologic driver of PSCC. However, the molecular details of the underlying carcinogenesis are understudied because of rare clinical specimens and missing cell lines. Here, we investigated if the expression of high-risk HPV16 oncogenes causes an augmentation of the Wnt pathway using unique HPV-positive penile cancer (PeCa) cell lines in monolayer and organotypic 3D raft cultures as well as tissue micro arrays containing clinical tissue specimens. The HPV oncoproteins enhanced the expression of Leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6) and the HPV-positive PeCa cells expressed a signature of Wnt target and stemness-associated genes. However, the notable lack of nuclear β-catenin in vitro and in situ raised the question if the enhanced expression of Wnt pathway factors is tantamount to an active Wnt signaling. Subsequent TOP-flash reporter assays revealed Wnt signaling as absent and not inducible by respective Wnt ligands in PeCa cell lines. The HPV-positive PeCa cells and especially HPV-positive PeCa specimens of the tumor core expressed the Wnt antagonist and negative feedback-regulator Dickkopf1 (DKK1). Subsequent neutralization experiments using PeCa cell line-conditioned media demonstrated that DKK1 is capable to impair ligand-induced Wnt signaling. While gene expression analyses suggested an augmented and active canonical Wnt pathway, the respective signaling was inhibited due to the endogenous expression of the antagonist DKK1. Subsequent TMA stainings indicated Dkk1 as linked with HPV-positivity and metastatic disease progression in PeCa suggesting potential as a prognostic marker. 相似文献
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Hong-Bin Wang Hong Wei Jin-Song Wang Lin Li An-Yue Chen Zhi-Gao Li 《生物化学与生物物理学报:疾病的分子基础》2019,1865(3):708-723
Breast cancer (BC)-related mortality is associated with the potential metastatic properties of the primary breast tumors. The following study was conducted with the main focus on the effect of LINC00518 on the growth and metastasis of BC epithelial cells via the Wnt signaling pathway through regulation of the methylation of CDX2 gene. Initially, differentially expressed long intergenic non-protein coding RNAs (lincRNAs) related to BC were screened out in the Cancer Genome Atlas (TCGA) database, after which we detected the LINC00518 expression and localization in BC tissues and cells. Then the CDX2 positive expression and methylation level were identified. The targeting relationship of LINC00518 and CDX2, and binding methyltransferase in the promoter region were examined. BC epithelial cell proliferation, colony formation ability, invasion, migration and apoptosis were further evaluated. The lincRNA expression data related to BC downloaded from the TCGA database revealed that there was a high expression of LINC00518 in BC, and a negative correlation between LINC00518 and CDX2. In addition, LINC00518 promotes CDX2 methylation by recruiting DNA methyltransferase through activating the Wnt signaling pathway. The down-regulation of LINC00518 inhibited proliferation, invasion, migration, and EMT of BC epithelial cells while enhancing apoptosis. The inhibitory effects of LINC00518 down-regulation was reversed by CDX2 down-regulation. In conclusion, our findings revealed that down-regulation of LINC00518 might have the ability to suppress BC progression by up-regulating CDX2 expression through the reduction of methylation and blockade of the Wnt signaling pathway, resulting in the inhibition of proliferation and promotion of apoptosis of BC epithelial cells. 相似文献
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Lin YC You L Xu Z He B Mikami I Thung E Chou J Kuchenbecker K Kim J Raz D Yang CT Chen JK Jablons DM 《Biochemical and biophysical research communications》2006,341(2):635-640
Aberrant activation of Wingless-type (Wnt) signaling pathway plays a critical role in oncogenesis of various human cancers. Wnt inhibitory factor-1 (WIF-1) is a secreted antagonist of Wnt signaling and acts through direct binding to Wnt in the extracellular space. Recently, we reported Wnt signaling in various human malignancies. In addition, we identified in lung cancer that WIF-1 is silenced due to promoter hypermethylation. In this study, we found constitutive activation of Wnt signaling and WIF-1 silencing in nasopharyngeal carcinoma (NPC) cell lines. Furthermore, by utilizing methylation-specific PCR and sequence analysis, we demonstrated that frequent hypermethylation of the WIF-1 promoter correlates with WIF-1 silencing in NPC cell lines. Our results indicate that aberrant Wnt signaling is a common event in NPC carcinogenesis linked with WIF-1 silencing in at least cell lines. Strategies targeting these molecules should be potentially promising in treating NPC. 相似文献
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Yun Liu Yue Chang Shuxiong Lu Yuan-Yuan Xiang 《Journal of cellular physiology》2019,234(7):11662-11669
Accumulating research works have reported that long noncoding RNAs (lncRNAs) are involved in various cancers, including cervical cancer. LncRNA DGCR5 has been identified in many cancers. However, the biological role of DGCR5 in cervical cancer remains barely known. We aimed to investigate the biological function of DGCR5 in cervical cancer progression. Here, in our current study, we observed that DGCR5 was downregulated in human cervical cancer cell lines (MS751, SiHa, HeLa, and HT-3) compared with the primary normal cervical squamous cells (NCSC1 and NCSC2). Then, DGCR5 was restrained by transfection with lenti-virus-short hairpin RNA (LV-shRNA) while induced by LV-DGCR5 in HeLa and C33A cells. Silence of DGCR5 obviously induced cervical cancer cell viability and cell proliferation. Reversely, upregulation of DGCR5 inhibited HeLa and C33A cell survival and proliferation. Furthermore, silencing of DGCR5 increased cervical cancer cell colony formation ability and decreased cell apoptosis, whereas its overexpression exhibited an opposite process. Moreover, DGCR5 suppressed migration and invasion capacity of cervical cancer cells. The Wnt signaling is integral in numerous biological processes. Here, we found that Wnt signaling was strongly activated in cervical cancer cells. Downregulation of DGCR5 contributed to cervical cancer progression by activating Wnt signaling. Subsequently, in vivo animal models were used to confirm that DGCR5 suppressed cervical cancer via targeting Wnt signaling. In conclusion, we reported that DGCR5 was involved in cervical cancer progression via modulating the Wnt pathway. 相似文献