scholarly journals m6A Modification: A Double-Edged Sword in Tumor Development

2021 ◽  
Vol 11 ◽  
Author(s):  
Runnan Gao ◽  
Mujie Ye ◽  
Baihui Liu ◽  
Meng Wei ◽  
Duan Ma ◽  
...  
Keyword(s):  
Dynamic Properties ◽  
Tumor Development ◽  
Tumor Formation ◽  
Cancer Development ◽  
Research Progress ◽  
Biological Processes ◽  
Rna Methylation ◽  
Anti Cancer ◽  
Elevated Expression

Modification of m6A, as the most abundant mRNA modification, plays diverse roles in various biological processes in eukaryotes. Emerging evidence has revealed that m6A modification is closely associated with the activation and inhibition of tumor pathways, and it is significantly linked to the prognosis of cancer patients. Aberrant reduction or elevated expression of m6A regulators and of m6A itself have been identified in numerous tumors. In this review, we give a description of the dynamic properties of m6A modification regulators, such as methyltransferases, demethylases, and m6A binding proteins, and indicate the value of the balance between these proteins in regulating the expression of diverse genes and the underlying effects on cancer development. Furthermore, we summarize the “dual-edged weapon” role of RNA methylation in tumor progression and discuss that RNA methylation can not only result in tumorigenesis but also lead to suppression of tumor formation. In addition, we summarize the latest research progress on small-molecule targeting of m6A regulators to inhibit or activate m6A. These studies indicate that restoring the balance of m6A modification via targeting specific imbalanced regulators may be a novel anti-cancer strategy.

scholarly journals The Role Of Nitric Oxide In Cancer Development & it`s Therapy

2020 ◽  
Vol 3 (1) ◽  
pp. 21-34
Author(s):  
Najlaa Qassim Muftin ◽  
Asma Jameil Al-Lamei ◽  
Suzanne Jubair ◽  
Abdalla Raied Jabber ◽  
Rasha Shakir Mahmood
Keyword(s):  
Nitric Oxide ◽  
Reactive Nitrogen Species ◽  
Tumor Formation ◽  
Cancer Development ◽  
Biological Processes ◽  
Nitrogen Species ◽  
Signal Molecule ◽  
Different Types ◽  
Proliferation And Metastasis

The Nitric oxide is a free radical belongs to reactive nitrogen species, acts as a signal molecule in many physiological and pathological processes as well as plays a significant role in a variety of biological processes including its action as a regulator to programmed cell death (apoptosis). In addition to its role in tumor formation, proliferation, and metastasis, Nitric oxide has also been stated to have tumoricidal effects. Therefore this review deals with the effect of nitric oxide on different types of cancer and its use in cancer drugs

NOB1: A Potential Biomarker or Target in Cancer

2019 ◽  
Vol 20 (10) ◽  
pp. 1081-1089
Author(s):  
Weiwei Ke ◽  
Zaiming Lu ◽  
Xiangxuan Zhao
Keyword(s):  
Cancer Treatment ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Binding Protein ◽  
Tumor Development ◽  
Anticancer Therapy ◽  
Research Progress ◽  
Normal Tissues ◽  
Potential Biomarker

Human NIN1/RPN12 binding protein 1 homolog (NOB1), an RNA binding protein, is expressed ubiquitously in normal tissues such as the lung, liver, and spleen. Its core physiological function is to regulate protease activities and participate in maintaining RNA metabolism and stability. NOB1 is overexpressed in a variety of cancers, including pancreatic cancer, non-small cell lung cancer, ovarian cancer, prostate carcinoma, osteosarcoma, papillary thyroid carcinoma, colorectal cancer, and glioma. Although existing data indicate that NOB1 overexpression is associated with cancer growth, invasion, and poor prognosis, the molecular mechanisms behind these effects and its exact roles remain unclear. Several studies have confirmed that NOB1 is clinically relevant in different cancers, and further research at the molecular level will help evaluate the role of NOB1 in tumors. NOB1 has become an attractive target in anticancer therapy because it is overexpressed in many cancers and mediates different stages of tumor development. Elucidating the role of NOB1 in different signaling pathways as a potential cancer treatment will provide new ideas for existing cancer treatment methods. This review summarizes the research progress made into NOB1 in cancer in the past decade; this information provides valuable clues and theoretical guidance for future anticancer therapy by targeting NOB1.

Potential of Mesenchymal Stem Cells in Anti-Cancer Therapies

2020 ◽  
Vol 15 (6) ◽  
pp. 482-491 ◽  
Author(s):  
Milena Kostadinova ◽  
Milena Mourdjeva
Keyword(s):  
Cancer Cells ◽  
Small Population ◽  
Tumor Formation ◽  
Bioactive Molecules ◽  
Cancer Therapies ◽  
New Methods ◽  
Cycle Arrest ◽  
Anti Cancer ◽  
Blocking Mechanisms

Mesenchymal stem/stromal cells (MSCs) are localized throughout the adult body as a small population in the stroma of the tissue concerned. In injury, tissue damage, or tumor formation, they are activated and leave their niche to migrate to the site of injury, where they release a plethora of growth factors, cytokines, and other bioactive molecules. With the accumulation of data about the interaction between MSCs and tumor cells, the dualistic role of MSCs remains unclear. However, a large number of studies have demonstrated the natural anti-tumor properties inherent in MSCs, so this is the basis for intensive research for new methods using MSCs as a tool to suppress cancer cell development. This review focuses specifically on advanced approaches in modifying MSCs to become a powerful, precision- targeted tool for killing cancer cells, but not normal healthy cells. Suppression of tumor growth by MSCs can be accomplished by inducing apoptosis or cell cycle arrest, suppressing tumor angiogenesis, or blocking mechanisms mediating metastasis. In addition, the chemosensitivity of cancer cells may be increased so that the dose of the chemotherapeutic agent used could be significantly reduced.

scholarly journals BAX requires VDAC2 to mediate apoptosis and to limit tumor development

2018 ◽  
Author(s):  
Hui San Chin ◽  
Mark F. van Delft ◽  
Robert L. Ninnis ◽  
Mark X. Li ◽  
Iris K. L. Tan ◽  
...  
Keyword(s):  
Tumor Development ◽  
Anion Channel ◽  
Tumor Formation ◽  
Cytotoxic Action ◽  
Voltage Dependent Anion Channel ◽  
Genome Wide ◽  
Anti Cancer ◽  
Voltage Dependent ◽  
Genetic Deletion ◽  
First Time

AbstractIntrinsic apoptosis is critical for normal physiology including the prevention of tumor formation. BAX and BAK are essential for mediating this process and for the cytotoxic action of many anticancer drugs. BAX and BAK are thought to act in a functionally redundant manner and are considered to be regulated similarly. From an unbiased genome-wide CRISPR/Cas9 screen, we identified VDAC2 (voltage-dependent anion channel 2) as essential for BAX, but not BAK, to function. The genetic deletion of VDAC2 abrogated the association of BAX and BAK with mitochondrial complexes that contain VDAC1, VDAC2 and VDAC3. By disrupting its localization to mitochondria, BAX is rendered completely ineffective. Moreover, we defined an interface unique to VDAC2 that is required to drive BAX activity. Consequently, interfering with this interaction or deleting VDAC2 phenocopied the loss of BAX, including impairing the killing of tumor cells by anti-cancer agents such as the BCL-2 inhibitor venetoclax. Furthermore, the ability of BAX to prevent tumor formation was attenuated in the absence of VDAC2. Taken together, our studies show for the first time that BAX-mediated apoptosis, but not BAK-mediated apoptosis, is critically dependent on VDAC2, hence revealing the differential regulation of BAX and BAK.

scholarly journals Role of Main RNA Methylation in Hepatocellular Carcinoma: N6-Methyladenosine, 5-Methylcytosine, and N1-Methyladenosine

2021 ◽  
Vol 9 ◽  
Author(s):  
Yating Xu ◽  
Menggang Zhang ◽  
Qiyao Zhang ◽  
Xiao Yu ◽  
Zongzong Sun ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cellular Differentiation ◽  
Molecular Mechanisms ◽  
Gene Sequence ◽  
Epigenetic Modification ◽  
Biological Processes ◽  
Biological Functions ◽  
Rna Detection ◽  
Rna Methylation

RNA methylation is considered a significant epigenetic modification, a process that does not alter gene sequence but may play a necessary role in multiple biological processes, such as gene expression, genome editing, and cellular differentiation. With advances in RNA detection, various forms of RNA methylation can be found, including N6-methyladenosine (m6A), N1-methyladenosine (m1A), and 5-methylcytosine (m5C). Emerging reports confirm that dysregulation of RNA methylation gives rise to a variety of human diseases, particularly hepatocellular carcinoma. We will summarize essential regulators of RNA methylation and biological functions of these modifications in coding and noncoding RNAs. In conclusion, we highlight complex molecular mechanisms of m6A, m5C, and m1A associated with hepatocellular carcinoma and hope this review might provide therapeutic potent of RNA methylation to clinical research.

TMOD-26. MYC OVEREXPRESSION AND SMARCA4 LOSS IN GRANULE CELL PRECURSORS COOPERATE TO DRIVE MEDULLOBLASTOMA FORMATION IN MICE

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi221-vi221
Author(s):  
Carolin Göbel ◽  
Dörthe Holdhof ◽  
Melanie Schoof ◽  
Catena Kresbach ◽  
Ulrich Schüller
Keyword(s):  
Granule Cell ◽  
Clinical Course ◽  
Tumor Development ◽  
Tumor Formation ◽  
Human Group ◽  
Group 4 ◽  
Small Cohort ◽  
Group 3 ◽  
Granule Cell Precursors

Abstract Mutations in SMARCA4 are frequently identified in medulloblastoma, the most common pediatric malignant brain tumor. However, the functional significance of these mutations and their suitability as a therapeutic target remain largely unclear. Medulloblastomas are divided into 4 subgroups according to their localization, molecular biology, and clinical course: WNT, SHH, Group 3, and Group 4. Group 3 medulloblastomas are associated with the poorest outcome and frequently show amplifications of the oncogene MYC. Additionally, SMARCA4 is mutated in around 15 % of cases. The few mouse models developed for this entity so far all involve the overexpression of MYC, mostly in combination with other drivers. However, none of these models include alterations in Smarca4. In our approach, we combined an overexpression of MYC with a loss of SMARCA4 in granule cell precursors, which successfully induced tumor formation in mice. For this purpose, granule cell precursors were isolated from 7-day-old Math1-creER T2 ::Smarca4 fl/fl pups after tamoxifen induced loss of SMARCA4. MYC overexpression was achieved by lentiviral transduction and transduced cells were transplanted into immunodeficient CD1 nu/nu mice. Preliminary results within a small cohort showed tumor formation in 5/19 transplanted mice (26 %) after 6 months. Immunohistochemically, tumors all stained negative for SMARCA4. In a next step, additional cohorts will elucidate if tumor development is indeed accelerated by or even dependent on the loss of SMARCA4. Additionally, the neoplastic potential of tumor cells will be verified with the aid of secondary recipient mice. To evaluate to what extent the generated tumors are comparable to human Group 3 medulloblastomas, tumors will be extensively analyzed on a morphological, transcriptional, and epigenetic level. Altogether, we hope to establish a suitable mouse model for SMARCA4 mutated Group 3 medulloblastoma that will help to elucidate the role of SMARCA4 in tumor development and to identify new therapeutic targets.

scholarly journals Pathogen-Induced Epigenetic Modifications in Cancers: Implications for Prevention, Detection and Treatment of Cancers in Africa

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6051
Author(s):  
Alexandra Lindsey Djomkam Zune ◽  
Charles Ochieng’ Olwal ◽  
Kesego Tapela ◽  
Oloche Owoicho ◽  
Nora Nghochuzie Nganyewo ◽  
...  
Keyword(s):  
Epigenetic Modifications ◽  
Tumor Formation ◽  
Cancer Development ◽  
Extrinsic Factors ◽  
Cancer Epigenetics ◽  
Public Health Burden ◽  
Cancer Management ◽  
Body Of Knowledge ◽  
Epigenetic Patterns

Cancer is a major public health burden worldwide. Tumor formation is caused by multiple intrinsic and extrinsic factors. Many reports have demonstrated a positive correlation between the burden of infectious pathogens and the occurrence of cancers. However, the mechanistic link between pathogens and cancer development remains largely unclear and is subject to active investigations. Apart from somatic mutations that have been widely linked with various cancers, an appreciable body of knowledge points to alterations of host epigenetic patterns as key triggers for cancer development. Several studies have associated various infectious pathogens with epigenetic modifications. It is therefore plausible to assume that pathogens induce carcinogenesis via alteration of normal host epigenetic patterns. Thus, Africa with its disproportionate burden of infectious pathogens is threatened by a dramatic increase in pathogen-mediated cancers. To curb the potential upsurge of such cancers, a better understanding of the role of tropical pathogens in cancer epigenetics could substantially provide resources to improve cancer management among Africans. Therefore, this review discusses cancer epigenetic studies in Africa and the link between tropical pathogens and cancer burden. In addition, we discuss the potential mechanisms by which pathogens induce cancers and the opportunities and challenges of tropical pathogen-induced epigenetic changes for cancer prevention, detection and management.

scholarly journals Hiding in Plain Sight: Epigenetic Plasticity in Drug-Induced Tumor Evolution

2019 ◽  
Vol 12 ◽  
pp. 251686571987076 ◽  
Author(s):  
Ankur Sharma
Keyword(s):  
Drug Resistance ◽  
Clonal Selection ◽  
Tumor Development ◽  
Standard Of Care ◽  
Tumor Evolution ◽  
Drug Induced ◽  
Epigenetic State ◽  
Anti Cancer ◽  
Selection Of

Cancer is a heterogeneous disease with key differences at the cellular and molecular levels. Acquisition of these differences during the course of tumor development manifests into functional and phenotypic heterogeneity leading to tumor diversity, also referred to as intra-tumor heterogeneity (ITH). Within a tumor, there are subpopulations of cells capable of tumor initiation and maintenance. These cells often exhibit resistance to standard-of-care anti-cancer drugs. However, the role of various subpopulations (clones) in drug resistance remains to be investigated. Moreover, the jury is still out about whether drug resistance is a result of clonal selection of preexisting cells, or the cells acquire resistance by dynamic re-wiring of their epigenome. Therefore, we investigated the drug-induced tumor evolution in patient-derived primary cells of head and neck squamous cell carcinoma. Our data demonstrated the role of a preexisting poised epigenetic state in drug-induced adaptive evolution of tumor cells. Importantly, the combination of chemotherapy and epigenetic inhibitors can prevent/delay drug-induced tumor evolution.

scholarly journals The dual role of filamin A in cancer: can't live with (too much of) it, can't live without it

2013 ◽  
Vol 20 (6) ◽  
pp. R341-R356 ◽  
Author(s):  
Rosalinda M Savoy ◽  
Paramita M Ghosh
Keyword(s):  
Tumor Formation ◽  
Dual Role ◽  
Cancer Development ◽  
Vascular Endothelial ◽  
Filamin A ◽  
Invasion And Metastasis ◽  
Promoting Effect ◽  
Metastasis Development ◽  
Endothelial Growth Factor

Filamin A (FlnA) has been associated with actin as cytoskeleton regulator. Recently its role in the cell has come under scrutiny for FlnA's involvement in cancer development. FlnA was originally revealed as a cancer-promoting protein, involved in invasion and metastasis. However, recent studies have also found that under certain conditions, it prevented tumor formation or progression, confusing the precise function of FlnA in cancer development. Here, we try to decipher the role of FlnA in cancer and the implications for its dual role. We propose that differences in subcellular localization of FlnA dictate its role in cancer development. In the cytoplasm, FlnA functions in various growth signaling pathways, such as vascular endothelial growth factor, in addition to being involved in cell migration and adhesion pathways, such as R-Ras and integrin signaling. Involvement in these pathways and various others has shown a correlation between high cytoplasmic FlnA levels and invasive cancers. However, an active cleaved form of FlnA can localize to the nucleus rather than the cytoplasm and its interaction with transcription factors has been linked to a decrease in invasiveness of cancers. Therefore, overexpression of FlnA has a tumor-promoting effect, only when it is localized to the cytoplasm, whereas if FlnA undergoes proteolysis and the resulting C-terminal fragment localizes to the nucleus, it acts to suppress tumor growth and inhibit metastasis. Development of drugs to target FlnA and cause cleavage and subsequent localization to the nucleus could be a new and potent field of research in treating cancer.

Matrix metalloproteinases-2, -3, and -9 secreted by explants of benign and malignant lesions of the uterine cervix

2004 ◽  
Vol 14 (2) ◽  
pp. 333-340 ◽  
Author(s):  
J. Argüello-Ramírez ◽  
E. PÉREZ-CÁRDENAS ◽  
R. Delgado-Chávez ◽  
G. Solorza-Luna ◽  
S. Villa-Treviño ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Poor Prognosis ◽  
Critical Role ◽  
Tumor Development ◽  
Cervical Lesions ◽  
Elevated Expression ◽  
Human Carcinomas ◽  
Malignant Lesions ◽  
Biological Development

Elevated expression of matrix metalloproteinases (MMPs) plays a critical role in extracellular matrix (EM) degradation in tumor development and prognosis of different human carcinomas. In cervical carcinoma (Ce Ca), the role of these proteinases in the biological development of this neoplasm is controversial. In the present study, we compared the secretion of MMP-2, MMP-3 and MMP-9 among 29 benign and premalignant cervical lesions (cervicitis and cervical intraepithelial neoplasias) and 46 tumoral explants of Ce Ca. The explants were cultured for 48 h. The gelatinases secreted into conditioned medium were revealed by zymography and quantified by densitometry. The results showed high levels of MMP-3 and MMP-9 in tumoral explants. In contrast, only the pro-MMP-2 was higher in benign cervical lesions, although both active and inactive MMP-2 species are associated with advanced clinical stages in tumoral samples, and only the secretion of MMP-3 was associated with unresponsiveness to radiotherapy. We can conclude that the expression of MMPs is related to the invasive process in Ce Ca and suggest that they may play a role in degradation of the EM during local invasion. In addition, MMP-3 secretion could be a marker of poor prognosis in Ce Ca.

Sign in / Sign up

Export Citation Format

Share Document