scholarly journals CDK5RAP3 Participates in Autophagy Regulation and Is Downregulated in Renal Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Jun Li ◽  
Xinyi Hu ◽  
Ming Su ◽  
Hongliang Shen ◽  
Wei Qiu ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Cell Viability ◽  
Cancer Cells ◽  
Renal Cancer ◽  
Significant Inhibition ◽  
Regulatory Subunit ◽  
Putative Tumor Suppressor ◽  
Cancer Tissues ◽  
P Cells ◽  
Urological Tumors

Renal cancer is one of the most common malignant urological tumors; however, its diagnosis and treatment are not well established. In the present study, we identified that CDK5 regulatory subunit-associated protein 3 (CDK5RAP3), a putative tumor suppressor in many cancers, was downregulated in renal cancer tissues. Through loss- and gain-of-function experiments, we observed that the action of CDK5RAP3 in renal cancer cells was different in Caki-1 and 769-P cell lines. Knockdown of endogenous CDK5RAP3 in Caki-1 slightly increased cell viability, whereas overexpression of CDK5RAP3 in 769-P cells inhibited cell viability. In addition, we observed that CDK5RAP3 participated in the regulation of autophagy in renal cancer. Knockdown of CDK5RAP3 induced significant inhibition of autophagy in Caki-1 cells but not in 769-P cells. In contrast, overexpression of CDK5RAP3 significantly activated autophagy in 769-P cells, as evidenced by increased LC3-II levels. However, the LC3-II could not be altered by CDK5RAP3 overexpression in Caki-1 cells. These findings demonstrated that CDK5RAP3 is downregulated in renal cancer and may be associated with autophagy.

The tumor suppressor LZTS2 functions through the cellular samurai Katanin

2009 ◽  
Vol 4 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Yoshiro Maru
Keyword(s):  
Cell Cycle ◽  
Tumor Suppressor ◽  
Leucine Zipper ◽  
Biological Effects ◽  
Regulatory Subunit ◽  
Future Research ◽  
Central Spindle ◽  
Microtubule Severing ◽  
Putative Tumor Suppressor ◽  
Potential Area

AbstractThe leucine zipper putative tumor suppressor (LZTS) 2 is frequently and specifically found in LOH (loss of heterozygosity) analysis in cancer. Different from other LZTS family members, it regulates the microtubule-severing protein Katanin by binding the p80 regulatory subunit of Katanin and inhibiting its interaction with microtubules. At specific phases of the cell cycle, LZTS2 suppresses cell migration and establishes proper central spindle assembly for cytokinesis. Importantly, those biological effects are mediated by the inhibitory activity of LZTS2 on Katanin. LZTS2 binding to Katanin also plays a role in Katanin transport to the midbody to control proper abscission. Therapeutic applications of the interaction between LZTS2 and Katanin in tumor cells are a potential area for future research.

scholarly journals von Hippel-Lindau Tumor Suppressor Protein Regulates the Assembly of Intercellular Junctions in Renal Cancer Cells through Hypoxia-Inducible Factor–Independent Mechanisms

2006 ◽  
Vol 66 (3) ◽  
pp. 1553-1560 ◽  
Author(s):  
Maria J. Calzada ◽  
Miguel A. Esteban ◽  
Monica Feijoo-Cuaresma ◽  
Maria C. Castellanos ◽  
Salvador Naranjo-Suárez ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Cancer Cells ◽  
Renal Cancer ◽  
Hypoxia Inducible Factor ◽  
Intercellular Junctions ◽  
Tumor Suppressor Protein ◽  
Von Hippel Lindau

scholarly journals NRF3-POMP-20S Proteasome Assembly Axis Promotes Cancer Development via Ubiquitin-Independent Proteolysis of p53 and Retinoblastoma Protein

2020 ◽  
Vol 40 (10) ◽  
Author(s):  
Tsuyoshi Waku ◽  
Nanami Nakamura ◽  
Misaki Koji ◽  
Hidenori Watanabe ◽  
Hiroki Katoh ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Cancer Cells ◽  
Proteasome Inhibitor ◽  
Rectal Adenocarcinoma ◽  
26S Proteasome ◽  
Cancer Development ◽  
20S Proteasome ◽  
Cancer Cell Growth ◽  
Protein Levels ◽  
Cancer Tissues

ABSTRACT Proteasomes are essential protease complexes that maintain cellular homeostasis, and aberrant proteasomal activity supports cancer development. The regulatory mechanisms and biological function of the ubiquitin-26S proteasome have been studied extensively, while those of the ubiquitin-independent 20S proteasome system remain obscure. Here, we show that the cap ’n’ collar (CNC) family transcription factor NRF3 specifically enhances 20S proteasome assembly in cancer cells and that 20S proteasomes contribute to colorectal cancer development through ubiquitin-independent proteolysis of the tumor suppressor p53 and retinoblastoma (Rb) proteins. The NRF3 gene is highly expressed in many cancer tissues and cell lines and is important for cancer cell growth. In cancer cells, NRF3 upregulates the assembly of the 20S proteasome by directly inducing the gene expression of the 20S proteasome maturation protein POMP. Interestingly, NRF3 knockdown not only increases p53 and Rb protein levels but also increases p53 activities for tumor suppression, including cell cycle arrest and induction of apoptosis. Furthermore, protein stability and cell viability assays using two distinct proteasome inhibitor anticancer drugs, the 20S proteasome inhibitor bortezomib and the ubiquitin-activating enzyme E1 inhibitor TAK-243, show that the upregulation of the NRF3-POMP axis leads to ubiquitin-independent proteolysis of p53 and Rb and to impaired sensitivity to bortezomib but not TAK-243. More importantly, the NRF3-POMP axis supports tumorigenesis and metastasis, with higher NRF3/POMP expression levels correlating with poor prognoses in patients with colorectal or rectal adenocarcinoma. These results suggest that the NRF3-POMP-20S proteasome assembly axis is significant for cancer development via ubiquitin-independent proteolysis of tumor suppressor proteins.

scholarly journals UCHL1 Is a Putative Tumor Suppressor in Ovarian Cancer Cells and Contributes to Cisplatin Resistance

2013 ◽  
Vol 4 (8) ◽  
pp. 662-670 ◽  
Author(s):  
Chengmeng Jin ◽  
Wei Yu ◽  
Xiaoyan Lou ◽  
Fan Zhou ◽  
Xu Han ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Cisplatin Resistance ◽  
Ovarian Cancer Cells ◽  
Putative Tumor Suppressor

scholarly journals TMIGD1, a Putative Tumor Suppressor, Induces G2-M Cell Cycle Checkpoint Arrest in Colon Cancer Cells

2020 ◽  
Author(s):  
Kyle De La Cena ◽  
Rachel Xi-Yeen Ho ◽  
Razie Amraei ◽  
Nick Woolf ◽  
Joseph Y. Tashjian ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Cell Cycle Checkpoint ◽  
Colon Cancer Cells ◽  
M Cell ◽  
Putative Tumor Suppressor ◽  
Cycle Checkpoint

scholarly journals MBD1 promotes the malignant behavior of gallbladder cancer cells and induces chemotherapeutic resistance to gemcitabine

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Liu Wensheng ◽  
Zhang Bo ◽  
Hu Qiangsheng ◽  
Xu Wenyan ◽  
Ji Shunrong ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cell Viability ◽  
Gallbladder Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Development ◽  
Human Gallbladder ◽  
Mesenchymal Transition ◽  
Cancer Tissues

Abstract Background Methyl-CpG binding domain protein 1 (MBD1), which couples DNA methylation to transcriptional repression, has been implicated in transcriptional regulation, heterochromatin formation, genomic stability, cell cycle progression and development. It has also been proven that MBD1 is involved in tumor development and progression. However, whether MBD1 is involved in tumorigenesis, especially in gallbladder cancer, is totally unknown. Methods Human GBC-SD and SGC996 cells were used to perform experiments. Invasion, wound healing and colony formation assays were performed to evaluate cell viability. A CCK-8 assay was performed to assess gallbladder cancer cell viability after gemcitabine treatment. Western blot analysis was used to evaluate changes in protein expression. Human gallbladder cancer tissues and adjacent nontumor tissues were subjected to immunohistochemical staining to detect protein expression. Results We found that MBD1 expression was significantly upregulated in gallbladder cancer tissues compared with that in surrounding normal tissues according to immunohistochemical analysis of 84 surgically resected gallbladder cancer specimens. These data also indicated that higher MBD1 expression was correlated with lymph node metastasis and poor survival in gallbladder cancer patients. Overexpression and deletion in vitro validated MBD1 as a potent oncogene promoting malignant behaviors in gallbladder cancer cells, including invasion, proliferation and migration, as well as epithelial–mesenchymal transition. Studies have demonstrated that epithelial–mesenchymal transition is common in gallbladder cancer, and it is well known that drug resistance and epithelial–mesenchymal transition are very closely correlated. Herein, our data show that targeting MBD1 restored gallbladder cancer cell sensitivity to gemcitabine chemotherapy. Conclusions Taken together, the results of our study revealed a novel function of MBD1 in gallbladder cancer tumor development and progression through participation in the gallbladder cancer epithelial–mesenchymal transition program, which is involved in resistance to gemcitabine chemotherapy. Thus, MBD1 may be a potential therapeutic target for gallbladder cancer.

Synthesis of Some Benzimidazole-derived Molecules and their Effects on PARP-1 Activity and MDA-MB-231, MDA-MB-436, MDA-MB-468 Breast Cancer Cell Viability

2020 ◽  
Vol 20 (14) ◽  
pp. 1728-1738
Author(s):  
A. Selen Gurkan-Alp ◽  
Mehmet Alp ◽  
Arzu Z. Karabay ◽  
Asli Koc ◽  
Erdem Buyukbingol
Keyword(s):  
Breast Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Fibroblast Cell ◽  
Significant Inhibition ◽  
Anticancer Activities ◽  
L929 Cells ◽  
Underlying Mechanisms ◽  
Substituted Piperazine ◽  
Parp 1

Background: Poly (ADP-ribosyl) polymerase-1 (PARP-1) inhibitors are compounds that are used to treat cancers, which are defective in DNA-repair and DNA Damage-Response (DDR) pathways. Objective: In this study, a series of potential PARP-1 inhibitor substituted (piperazine-1-carbonyl)phenyl)-1Hbenzo[ d]imidazole-4-carboxamide compounds were synthesised and tested for their PARP-1 inhibitory and anticancer activities. Methods: Compounds were tested by cell-free colorimetric PARP-1 activity and MTT assay in MDA-MB-231, MDA-MB-436, MDA-MB-468 breast cancer, and L929 fibroblast cell lines. Results: Our results showed that compound 6a inhibited viability in MDA-MB-231 and MDA-MB-468 cells whereas 8a inhibited viability in MDA-MB-468 cells. Compound 6b significantly inhibited cell viability in tested cancer cells. However, 6b exhibited toxicity in L929 cells, whereas 6a and 8a were found to be non-toxic for L929 cells. Compounds 6a, 6b and 8a exhibited significant inhibition of PARP-1 activity. Conclusion: These three compounds exhibited PARP-1 inhibitory activities and anticancer effects on breast cancer cells, and further research will enlighten the underlying mechanisms of their effects.

Sevoflurane Inhibits Growth and Metastasis of Cervical Cancer Through Up-Regulating miR-203 by Targeting Tumor Protein Translationally Controlled 1

2020 ◽  
Vol 10 (6) ◽  
pp. 874-883
Author(s):  
Li Zhang ◽  
Shiyou Wei ◽  
Zhenkai Xu ◽  
Wen Sun ◽  
Lihua Hang
Keyword(s):  
Cervical Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Target Genes ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Reporter System ◽  
Cervical Cancer Cells ◽  
Induced Apoptosis ◽  
Cancer Tissues

Background: Cervical cancer is a type of malignancy with high incidence and high mortality in women all over the world. Recent findings revealed the role of sevoflurane in the inhibition of development of various cancer types. This study aimed to explore whether sevoflurane could suppress cells proliferation and metastasis through adjusting miR-203 expression in cervical cancer. Methods: The effects of sevoflurane on HeLa cell viability was assessed using CCK-8 assay. miR-203 level in Hela cells was determined by qRT-PCR. In addition, cells apoptosis, migration and invasion were evaluated using flow cytometry and transwell analysis respectively after sevoflurane treatment or miR-203 expression changes. Bioinformatics software (TargetScan) was used to predict the potential target genes for miR-203 and the prediction was validated using dual-luciferase reporter system. Results: Sevoflurane effectively inhibited cell viability, metastasis and stimulated apoptosis in cervical cancer. miR-203 demonstrated a low expression in cervical cancer tissues and cells and sevoflurane significantly up-regulated miR-203 expression in cervical cancer cells. Upregulation of miR-203 significantly suppressed cell growth and metastasis and induced apoptosis, while down-regulation of miR-203 presented the opposite effects in cervical cancer cells. In addition, the inhibitory effects of sevoflurane were eliminated by down-regulating miR-203 in cervical cancer cells. In addition, TPT1 was confirmed as a target gene for miR-203. Conclusion: Sevoflurane inhibited cervical cancer cells viability and metastasis through up-regulation of miR-203 expression by targeting TPT1.

scholarly journals MP16-06 PUTATIVE TUMOR SUPPRESSOR ELL2 IS REQUIRED FOR PROLIFERATION AND SURVIVAL OF AR-NEGATIVE PROSTATE CANCER CELLS

2020 ◽  
Vol 203 ◽  
pp. e216
Author(s):  
Zhi Wang* ◽  
Laura E. Pascal ◽  
Uma R Chandran ◽  
Srilakshmi Chaparala ◽  
Shidong Lyu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Prostate Cancer Cells ◽  
Putative Tumor Suppressor

scholarly journals Synthetic circular miR-21 RNA decoys enhance tumor suppressor expression and impair tumor growth in mice

NAR Cancer ◽  
2020 ◽  
Vol 2 (3) ◽  
Author(s):  
Simon Müller ◽  
Alice Wedler ◽  
Janina Breuer ◽  
Markus Glaß ◽  
Nadine Bley ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Circular Rna ◽  
Significant Inhibition ◽  
Circular Rnas ◽  
Cell Vitality ◽  
Inhibition Of Tumor Growth ◽  
Functional Relevance

Abstract Naturally occurring circular RNAs efficiently impair miRNA functions. Synthetic circular RNAs may thus serve as potent agents for miRNA inhibition. Their therapeutic effect critically relies on (i) the identification of optimal miRNA targets, (ii) the optimization of decoy structures and (iii) the development of efficient formulations for their use as drugs. In this study, we extensively explored the functional relevance of miR-21-5p in cancer cells. Analyses of cancer transcriptomes reveal that miR-21-5p is the by far most abundant miRNA in human cancers. Deletion of the MIR21 locus in cancer-derived cells identifies several direct and indirect miR-21-5p targets, including major tumor suppressors with prognostic value across cancers. To impair miR-21-5p activities, we evaluate synthetic, circular RNA decoys containing four repetitive binding elements. In cancer cells, these decoys efficiently elevate tumor suppressor expression and impair tumor cell vitality. For their in vivo delivery, we for the first time evaluate the formulation of decoys in polyethylenimine (PEI)-based nanoparticles. We demonstrate that PEI/decoy nanoparticles lead to a significant inhibition of tumor growth in a lung adenocarcinoma xenograft mouse model via the upregulation of tumor suppressor expression. These findings introduce nanoparticle-delivered circular miRNA decoys as a powerful potential therapeutic strategy in cancer treatment.

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