scholarly journals Functional Interaction among lncRNA HOTAIR and MicroRNAs in Cancer and Other Human Diseases

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 570
Author(s):  
Monica Cantile ◽  
Maurizio Di Bonito ◽  
Maura Tracey De Bellis ◽  
Gerardo Botti
Keyword(s):  
Target Genes ◽  
Predictive Biomarker ◽  
Human Diseases ◽  
Cancer Development ◽  
Metastatic Progression ◽  
Functional Interaction ◽  
Cellular Processes ◽  
Regulatory Processes ◽  
Cancer Initiation ◽  
Lncrna Hotair

LncRNAs are a class of non-coding RNAs mostly involved in regulation of cancer initiation, metastatic progression, and drug resistance, through participation in post-transcription regulatory processes by interacting with different miRNAs. LncRNAs are able to compete with endogenous RNAs by binding and sequestering miRNAs and thereby regulating the expression of their target genes, often represented by oncogenes. The lncRNA HOX transcript antisense RNA (HOTAIR) represents a diagnostic, prognostic, and predictive biomarker in many human cancers, and its functional interaction with miRNAs has been described as crucial in the modulation of different cellular processes during cancer development. The aim of this review is to highlight the relation between lncRNA HOTAIR and different microRNAs in human diseases, discussing the contribution of these functional interactions, especially in cancer development and progression.

scholarly journals Inhibition of BET Proteins and Histone Deacetylase (HDACs): Crossing Roads in Cancer Therapy

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 304 ◽  
Author(s):  
Gloria Manzotti ◽  
Alessia Ciarrocchi ◽  
Valentina Sancisi
Keyword(s):  
Cancer Therapy ◽  
Histone Deacetylases ◽  
Target Genes ◽  
State Of The Art ◽  
Regulatory Elements ◽  
Functional Interaction ◽  
Cellular Processes ◽  
Silent Genes ◽  
Dual Inhibition ◽  
Chromatin Acetylation

Histone DeACetylases (HDACs) are enzymes that remove acetyl groups from histones and other proteins, regulating the expression of target genes. Pharmacological inhibition of these enzymes re-shapes chromatin acetylation status, confusing boundaries between transcriptionally active and quiescent chromatin. This results in reinducing expression of silent genes while repressing highly transcribed genes. Bromodomain and Extraterminal domain (BET) proteins are readers of acetylated chromatin status and accumulate on transcriptionally active regulatory elements where they serve as scaffold for the building of transcription-promoting complexes. The expression of many well-known oncogenes relies on BET proteins function, indicating BET inhibition as a strategy to counteract their activity. BETi and HDACi share many common targets and affect similar cellular processes to the point that combined inhibition of both these classes of proteins is regarded as a strategy to improve the effectiveness of these drugs in cancer. In this work, we aim to discuss the molecular basis of the interplay between HDAC and BET proteins, pointing at chromatin acetylation as a crucial node of their functional interaction. We will also describe the state of the art of their dual inhibition in cancer therapy. Finally, starting from their mechanism of action we will provide a speculative perspective on how these drugs may be employed in combination with standard therapies to improve effectiveness and/or overcome resistance.

scholarly journals LncRNA HOTAIR in Tumor Microenvironment: What Role?

2019 ◽  
Vol 20 (9) ◽  
pp. 2279 ◽  
Author(s):  
Gerardo Botti ◽  
Giosuè Scognamiglio ◽  
Gabriella Aquino ◽  
Giuseppina Liguori ◽  
Monica Cantile
Keyword(s):  
Gene Expression ◽  
Tumor Microenvironment ◽  
Intracellular Signaling ◽  
Regulation Of Gene Expression ◽  
Tumor Evolution ◽  
Metastatic Progression ◽  
Cellular Processes ◽  
Cellular Components ◽  
Lncrna Hotair

lncRNAs participate in many cellular processes, including regulation of gene expression at the transcriptional and post-transcriptional levels. In addition, many lncRNAs can contribute to the development of different human diseases including cancer. The tumor microenvironment (TME) plays an important role during tumor growth and metastatic progression, and most of these lncRNAs have a key function in TME intracellular signaling. Among the numerous identified lncRNAs, several experimental evidences have shown the fundamental role of the lncRNA HOTAIR in carcinogenesis, also highlighting its use as a circulating biomarker. In this review we described the contribution of HOTAIR in the TME modulation, highlighting its relation with cellular and non-cellular components during tumor evolution and progression.

scholarly journals Amyloid Precursor-Like Protein 2 Expression Increases during Pancreatic Cancer Development and Shortens the Survival of a Spontaneous Mouse Model of Pancreatic Cancer

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1535
Author(s):  
Brittany J. Poelaert ◽  
Shelby M. Knoche ◽  
Alaina C. Larson ◽  
Poomy Pandey ◽  
Parthasarathy Seshacharyulu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Mouse Model ◽  
Cancer Biology ◽  
The United States ◽  
Genetically Engineered ◽  
Cancer Development ◽  
Ductal Adenocarcinoma ◽  
Metastatic Progression ◽  
Primary Tumors ◽  
Cancer Initiation

In the United States, pancreatic cancer is a major cause of cancer-related deaths. Although substantial efforts have been made to understand pancreatic cancer biology and improve therapeutic efficacy, patients still face a bleak chance of survival. A greater understanding of pancreatic cancer development and the identification of novel treatment targets are desperately needed. Our analysis of gene expression data from patient samples showed an increase in amyloid precursor-like protein 2 (APLP2) expression within primary tumor epithelium relative to pancreatic intraepithelial neoplasia (PanIN) epithelial cells. Augmented expression of APLP2 in primary tumors compared to adjacent stroma was also observed. Genetically engineered mouse models of spontaneous pancreatic ductal adenocarcinoma were used to investigate APLP2′s role in cancer development. We found that APLP2 expression intensifies significantly during pancreatic cancer initiation and progression in the LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1-Cre (KPC) mouse model, as shown by immunohistochemistry analysis. In studies utilizing pancreas-specific heterozygous and homozygous knockout of APLP2 in the KPC mouse model background, we observed significantly prolonged survival and reduced metastatic progression of pancreatic cancer. These results demonstrate the importance of APLP2 in pancreatic cancer initiation and metastasis and indicate that APLP2 should be considered a potential therapeutic target for this disease.

scholarly journals Epigenetic Mechanisms of LncRNAs Binding to Protein in Carcinogenesis

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2925 ◽  
Author(s):  
Tae-Jin Shin ◽  
Kang-Hoon Lee ◽  
Je-Yoel Cho
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Target Genes ◽  
Cancer Development ◽  
Regulatory Function ◽  
Epigenetic Mechanisms ◽  
Cancer Initiation ◽  
Non Coding Rnas

Epigenetic dysregulation is an important feature for cancer initiation and progression. Long non-coding RNAs (lncRNAs) are transcripts that stably present as RNA forms with no translated protein and have lengths larger than 200 nucleotides. LncRNA can epigenetically regulate either oncogenes or tumor suppressor genes. Nowadays, the combined research of lncRNA plus protein analysis is gaining more attention. LncRNA controls gene expression directly by binding to transcription factors of target genes and indirectly by complexing with other proteins to bind to target proteins and cause protein degradation, reduced protein stability, or interference with the binding of other proteins. Various studies have indicated that lncRNA contributes to cancer development by modulating genes epigenetically and studies have been done to determine which proteins are combined with lncRNA and contribute to cancer development. In this review, we look in depth at the epigenetic regulatory function of lncRNAs that are capable of complexing with other proteins in cancer development.

scholarly journals Endolysosomal TRPMLs in Cancer

Biomolecules ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 65
Author(s):  
Mengnan Xu ◽  
Xian-Ping Dong
Keyword(s):  
Cancer Progression ◽  
Antitumor Immunity ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Nutrient Sensing ◽  
Human Diseases ◽  
Cancer Development ◽  
Cellular Processes ◽  
Multiple Processes ◽  
Transient Receptor

Lysosomes, the degradative endpoints and sophisticated cellular signaling hubs, are emerging as intracellular Ca2+ stores that govern multiple cellular processes. Dys-homeostasis of lysosomal Ca2+ is intimately associated with a variety of human diseases including cancer. Recent studies have suggested that the Ca2+-permeable channels Transient Receptor Potential (TRP) Mucolipins (TRPMLs, TRPML1-3) integrate multiple processes of cell growth, division and metabolism. Dysregulation of TRPMLs activity has been implicated in cancer development. In this review, we provide a summary of the latest development of TRPMLs in cancer. The expression of TRPMLs in cancer, TRPMLs in cancer cell nutrient sensing, TRPMLs-mediated lysosomal exocytosis in cancer development, TRPMLs in TFEB-mediated gene transcription of cancer cells, TRPMLs in bacteria-related cancer development and TRPMLs-regulated antitumor immunity are discussed. We hope to guide readers toward a more in-depth discussion of the importance of lysosomal TRPMLs in cancer progression and other human diseases.

MiRNA-145 and Its Direct Downstream Targets in Digestive System Cancers: A Promising Therapeutic Target

2020 ◽  
Vol 26 ◽  
Author(s):  
Yini Ma ◽  
Xiu Cao ◽  
Guojuan Shi ◽  
Tianlu Shi
Keyword(s):  
Digestive System ◽  
Target Genes ◽  
Malignant Neoplasm ◽  
Vital Role ◽  
Diagnostic Biomarkers ◽  
Cellular Processes ◽  
Promising Therapeutic Target ◽  
Direct Target ◽  
Potential Strategy

: MicroRNAs (miRNAs) play a vital role in the onset and development of many diseases, including cancers. Emerging evidence shows that numerous miRNAs have the potential to be used as diagnostic biomarkers for cancers, and miRNA-based therapy may be a promising therapy for the treatment of malignant neoplasm. MicroRNA-145 (miR-145) has been considered to play certain roles in various cellular processes, such as proliferation, differentiation and apoptosis, via modulating expression of direct target genes. Recent reports show that miR-145 participates in the progression of digestive system cancers, and plays crucial and novel roles for cancer treatment. In this review, we summarize the recent knowledge concerning the function of miR-145 and its direct targets in digestive system cancers. We discuss the potential role of miR-145 as valuable biomarkers for digestive system cancers and how miR-145 regulates these digestive system cancers via different targets to explore the potential strategy of targeting miR-145.

scholarly journals Lysosomal Calcium Channels in Autophagy and Cancer

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1299
Author(s):  
Yi Wu ◽  
Peng Huang ◽  
Xian-Ping Dong
Keyword(s):  
Calcium Channels ◽  
Cancer Progression ◽  
Human Cancer ◽  
Human Diseases ◽  
Cellular Processes ◽  
Cell Functions ◽  
Multiple Cell ◽  
Dependent Processes ◽  
Intracellular Messenger

Ca2+ is pivotal intracellular messenger that coordinates multiple cell functions such as fertilization, growth, differentiation, and viability. Intracellular Ca2+ signaling is regulated by both extracellular Ca2+ entry and Ca2+ release from intracellular stores. Apart from working as the cellular recycling center, the lysosome has been increasingly recognized as a significant intracellular Ca2+ store that provides Ca2+ to regulate many cellular processes. The lysosome also talks to other organelles by releasing and taking up Ca2+. In lysosomal Ca2+-dependent processes, autophagy is particularly important, because it has been implicated in many human diseases including cancer. This review will discuss the major components of lysosomal Ca2+ stores and their roles in autophagy and human cancer progression.

scholarly journals Epigenetic Methylations on N6-Adenine and N6-Adenosine with the same Input but Different Output

2019 ◽  
Vol 20 (12) ◽  
pp. 2931 ◽  
Author(s):  
Zhiqing Li ◽  
Ping Zhao ◽  
Qingyou Xia
Keyword(s):  
Genetic Information ◽  
Target Genes ◽  
Technological Development ◽  
Wide Spectrum ◽  
Functional Identification ◽  
Methyl Group ◽  
Cellular Processes ◽  
Dna And Rna ◽  
Future Challenges ◽  
Detection Strategies

Epigenetic modifications on individual bases in DNA and RNA can encode inheritable genetic information beyond the canonical bases. Among the nucleic acid modifications, DNA N6-methadenine (6mA) and RNA N6-methyladenosine (m6A) have recently been well-studied due to the technological development of detection strategies and the functional identification of modification enzymes. The current findings demonstrate a wide spectrum of 6mA and m6A distributions from prokaryotes to eukaryotes and critical roles in multiple cellular processes. It is interesting that the processes of modification in which the methyl group is added to adenine and adenosine are the same, but the outcomes of these modifications in terms of their physiological impacts in organisms are quite different. In this review, we summarize the latest progress in the study of enzymes involved in the 6mA and m6A methylation machinery, including methyltransferases and demethylases, and their functions in various biological pathways. In particular, we focus on the mechanisms by which 6mA and m6A regulate the expression of target genes, and we highlight the future challenges in epigenetic regulation.

scholarly journals First person – Magdalena Cardenas-Rodriguez

2021 ◽  
Vol 134 (14) ◽  
Keyword(s):  
Molecular Genetics ◽  
Small Gtpases ◽  
Early Career ◽  
Human Diseases ◽  
First Person ◽  
Research Assistant ◽  
Cellular Processes ◽  
Early Career Researchers ◽  
Genetic Compensation ◽  
Selection Of

ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Magdalena Cardenas-Rodriguez is first author on ‘ Genetic compensation for cilia defects in cep290 mutants by upregulation of cilia-associated small GTPases’, published in JCS. Magdalena is a research assistant in the lab of Jose Luis Badano at Human Molecular Genetics Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay, investigating the cellular processes that are altered in cilia-related human diseases.

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