scholarly journals Regulatory roles of RNA modifications in breast cancer

NAR Cancer ◽  
2021 ◽  
Vol 3 (3) ◽  
Author(s):  
Kanchan Kumari ◽  
Paula Groza ◽  
Francesca Aguilo
Keyword(s):  
Breast Cancer ◽  
Messenger Rna ◽  
Therapeutic Strategies ◽  
Rna Modifications ◽  
Breast Tumorigenesis ◽  
Cellular Processes ◽  
Trna Modifications ◽  
Expression Control ◽  
Gene Expression Control ◽  
Ribosomal Rrna

Abstract Collectively referred to as the epitranscriptome, RNA modifications play important roles in gene expression control regulating relevant cellular processes. In the last few decades, growing numbers of RNA modifications have been identified not only in abundant ribosomal (rRNA) and transfer RNA (tRNA) but also in messenger RNA (mRNA). In addition, many writers, erasers and readers that dynamically regulate the chemical marks have also been characterized. Correct deposition of RNA modifications is prerequisite for cellular homeostasis, and its alteration results in aberrant transcriptional programs that dictate human disease, including breast cancer, the most frequent female malignancy, and the leading cause of cancer-related death in women. In this review, we emphasize the major RNA modifications that are present in tRNA, rRNA and mRNA. We have categorized breast cancer-associated chemical marks and summarize their contribution to breast tumorigenesis. In addition, we describe less abundant tRNA modifications with related pathways implicated in breast cancer. Finally, we discuss current limitations and perspectives on epitranscriptomics for use in therapeutic strategies against breast and other cancers.

scholarly journals Oncogenic Signaling in Tumorigenesis and Applications of siRNA Nanotherapeutics in Breast Cancer

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 632 ◽  
Author(s):  
Nur Izyani Kamaruzman ◽  
Noraini Abd Aziz ◽  
Chit Laa Poh ◽  
Ezharul Hoque Chowdhury
Keyword(s):  
Breast Cancer ◽  
Signaling Pathways ◽  
Targeted Delivery ◽  
Therapeutic Strategies ◽  
Signaling Cascades ◽  
Breast Tumorigenesis ◽  
Oncogenic Signaling ◽  
Complementary Sequence ◽  
Genetic Manipulations ◽  
Oncogene Products

Overexpression of oncogenes and cross-talks of the oncoproteins-regulated signaling cascades with other intracellular pathways in breast cancer could lead to massive abnormal signaling with the consequence of tumorigenesis. The ability to identify the genes having vital roles in cancer development would give a promising therapeutics strategy in combating the disease. Genetic manipulations through siRNAs targeting the complementary sequence of the oncogenic mRNA in breast cancer is one of the promising approaches that can be harnessed to develop more efficient treatments for breast cancer. In this review, we highlighted the effects of major signaling pathways stimulated by oncogene products on breast tumorigenesis and discussed the potential therapeutic strategies for targeted delivery of siRNAs with nanoparticles in suppressing the stimulated signaling pathways.

scholarly journals Transcriptional Riboswitches Integrate Timescales for Bacterial Gene Expression Control

2021 ◽  
Vol 7 ◽  
Author(s):  
Catherine E. Scull ◽  
Shiba S. Dandpat ◽  
Rosa A. Romero ◽  
Nils G. Walter
Keyword(s):  
Gene Expression ◽  
Divalent Cations ◽  
Rna Aptamers ◽  
Signaling Cascades ◽  
Bacterial Gene ◽  
Cellular Processes ◽  
Expression Platform ◽  
Bacterial Gene Expression ◽  
Expression Control ◽  
Gene Expression Control

Transcriptional riboswitches involve RNA aptamers that are typically found in the 5′ untranslated regions (UTRs) of bacterial mRNAs and form alternative secondary structures upon binding to cognate ligands. Alteration of the riboswitch's secondary structure results in perturbations of an adjacent expression platform that controls transcription elongation and termination, thus turning downstream gene expression “on” or “off.” Riboswitch ligands are typically small metabolites, divalent cations, anions, signaling molecules, or other RNAs, and can be part of larger signaling cascades. The interconnectedness of ligand binding, RNA folding, RNA transcription, and gene expression empowers riboswitches to integrate cellular processes and environmental conditions across multiple timescales. For a successful response to an environmental cue that may determine a bacterium's chance of survival, a coordinated coupling of timescales from microseconds to minutes must be achieved. This review focuses on recent advances in our understanding of how riboswitches affect such critical gene expression control across time.

scholarly journals Loss of CNOT9 begets impairment in gastrulation leading to embryonic lethality

2020 ◽  
Author(s):  
Hemanta Sarmah ◽  
Kentaro Ito ◽  
Mari Kaneko ◽  
Takaya Abe ◽  
Tadashi Yamamoto
Keyword(s):  
Messenger Rna ◽  
Mrna Decay ◽  
Mutant Form ◽  
Wild Type ◽  
Expression Control ◽  
Gene Expression Control ◽  
Risc Complex ◽  
Extensive Cell Death ◽  
Extensive Cell

AbstractThe multi-subunit eukaryotic CCR4-NOT complex imparts gene expression control primarily via messenger RNA (mRNA) decay. Here, we present the role of subunit CNOT9 in target mRNA decay during embryonic development. CNOT9 null mice appear normal by the onset of gastrulation (E7.0), however, exhibit growth and differentiation defects accompanied by extensive cell death by embryonic day 9.5 (E9.5). Sox-2 Cre conditional CNOT9 knockout mice show almost identical phenotype with brief delay in onset and progression, suggesting defects to be epiblast-dominant. Among various identified targets, we show that Lefty2 mRNA expression is post-transcriptionally regulated by CNOT9. Lefty2 3’-UTR containing mRNA has significantly higher stability in cells expressing mutant form of CNOT9, relative to cells expressing wild-type CNOT9. In addition, CNOT9 primarily localizes within the cytoplasm and bridges interactions between the CCR4-NOT complex and miRNA-RISC complex in gastrulating embryos.

scholarly journals Methods for the analysis of transcriptome dynamics

2019 ◽  
Vol 8 (5) ◽  
pp. 597-612 ◽  
Author(s):  
Daniela F. Rodrigues ◽  
Vera M. Costa ◽  
Ricardo Silvestre ◽  
Maria L. Bastos ◽  
Félix Carvalho
Keyword(s):  
Gene Expression ◽  
Transcriptome Analysis ◽  
Messenger Rna ◽  
Noncoding Rna ◽  
Gene Expression Regulation ◽  
System Level ◽  
Rna Transcription ◽  
Expression Control ◽  
Gene Expression Control ◽  
Gene Expression Alterations

Abstract The transcriptome is the complete set of transcripts in a cell or tissue and includes ribosomal RNA (rRNA), messenger RNA (mRNA), transfer RNA (tRNA), and regulatory noncoding RNA. At steady-state, the transcriptome results from a compensatory variation of the transcription and decay rate to maintain the RNA concentration constant. RNA transcription constitutes the first stage in gene expression, and thus is a major and primary mode of gene expression control. Nevertheless, regulation of RNA decay is also a key factor in gene expression control, involving either selective RNA stabilization or enhanced degradation. Transcriptome analysis allows the identification of gene expression alterations, providing new insights regarding the pathways and mechanisms involved in physiological and pathological processes. Upon perturbation of cell homeostasis, rapid changes in gene expression are required to adapt to new conditions. Thus, to better understand the regulatory mechanisms associated with gene expression alterations, it is vital to acknowledge the relative contribution of RNA synthesis and decay to the transcriptome. To the toxicology field, the study of gene expression regulation mechanisms can help identify the early and mechanistic relevant cellular events associated with a particular response. This review aims to provide a critical comparison of the available methods used to analyze the contribution of RNA transcription and decay to gene expression dynamics. Notwithstanding, an integration of the data obtained is necessary to understand the entire repercussions of gene transcription changes at a system-level. Thus, a brief overview of the methods available for the integration and analysis of the data obtained from transcriptome analysis will also be provided.

scholarly journals Quantitative tRNA-sequencing uncovers metazoan tissue-specific tRNA regulation

2021 ◽  
Author(s):  
Otis Pinkard ◽  
Sean Mcfarland ◽  
Thomas Sweet ◽  
Jeff Coller
Keyword(s):  
Messenger Rna ◽  
Protein Production ◽  
Rna Stability ◽  
Amino Acid Identity ◽  
Rna Modifications ◽  
Transfer Rnas ◽  
Trna Modifications ◽  
Mammalian Tissues ◽  
Trna Sequencing ◽  
Regulatory Landscape

Abstract Transfer RNAs (tRNA) are quintessential in deciphering the genetic code; disseminating nucleic acid triplets into correct amino acid identity. While this decoding function is clear, an emerging theme is that tRNA abundance and functionality can powerfully impact protein production rate, folding, activity, and messenger RNA stability. Importantly, however, the expression pattern of tRNAs is obliquely known. Here we present Quantitative Mature tRNA sequencing (QuantM-tRNA seq), a technique to monitor tRNA abundance and sequence variants secondary to RNA modifications. With QuantM-tRNA seq we assess the tRNA transcriptome in mammalian tissues. We observe dramatic distinctions in isodecoder expression and known tRNA modifications between tissues. Remarkably, despite dramatic changes in tRNA isodecoder gene expression, the overall anticodon pool of each tRNA family is similar across tissues. These findings suggest that while anticodon pools appear to be buffered via an unknown mechanism, underlying transcriptomic and epitranscriptomic differences suggest a more complex tRNA regulatory landscape.

scholarly journals Epitranscriptomic Signatures in lncRNAs and Their Possible Roles in Cancer

Genes ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 52 ◽  
Author(s):  
Sorina Dinescu ◽  
Simona Ignat ◽  
Andreea Lazar ◽  
Carolina Constantin ◽  
Monica Neagu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Modifications ◽  
Chemical Modifications ◽  
Chemically Modified ◽  
Additional Layer ◽  
Expression Control ◽  
Gene Expression Control ◽  
Level Of Knowledge ◽  
Non Coding Rnas ◽  
And Function

In contrast to the amazing exponential growth in knowledge related to long non-coding RNAs (lncRNAs) involved in cell homeostasis or dysregulated pathological states, little is known so far about the links between the chemical modifications occurring in lncRNAs and their function. Generally, ncRNAs are post-transcriptional regulators of gene expression, but RNA modifications occurring in lncRNAs generate an additional layer of gene expression control. Chemical modifications that have been reported in correlation with lncRNAs include m6A, m5C and pseudouridylation. Up to date, several chemically modified long non-coding transcripts have been identified and associated with different pathologies, including cancers. This review presents the current level of knowledge on the most studied cancer-related lncRNAs, such as the metastasis associated lung adenocarcinoma transcript 1 (MALAT1), the Hox transcript antisense intergenic RNA (HOTAIR), or the X-inactive specific transcript (XIST), as well as more recently discovered forms, and their potential roles in different types of cancer. Understanding how these RNA modifications occur, and the correlation between lncRNA changes in structure and function, may open up new therapeutic possibilities in cancer.

scholarly journals SUMOylation Wrestles With the Occurrence and Development of Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Yuanyuan Qin ◽  
Hong Yuan ◽  
Xu Chen ◽  
Xinyi Yang ◽  
Zhengcao Xing ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Biological Activity ◽  
Effective Treatment ◽  
Cellular Localization ◽  
Therapeutic Strategies ◽  
Cellular Proteins ◽  
Important Process ◽  
Comprehensive Understanding ◽  
Detailed Mechanism ◽  
Cellular Processes

Breast cancer has the highest incidence among cancers and is the most frequent cause of death in women worldwide. The detailed mechanism of the pathogenesis of breast cancer has not been fully elucidated, and there remains a lack of effective treatment methods for the disease. SUMOylation covalently conjugates a large amount of cellular proteins, and affects their cellular localization and biological activity to participate in numerous cellular processes. SUMOylation is an important process and imbalance of SUMOylation results in the progression of human diseases. Increasing evidence shows that numerous SUMOylated proteins are involved in the occurrence and development of breast cancer. This review summarizes a series of studies on protein SUMOylation in breast cancer in recent years. The study of SUMOylated proteins provides a comprehensive understanding of the pathophysiology of breast cancer and provides evolving therapeutic strategies for the treatment of breast cancer.

scholarly journals Interleukin-34-CSF1R Signaling Axis Promotes Epithelial Cell Transformation and Breast Tumorigenesis

2021 ◽  
Vol 22 (5) ◽  
pp. 2711
Author(s):  
Muna Poudel ◽  
Garam Kim ◽  
Poshan Yugal Bhattarai ◽  
Jin-Young Kim ◽  
Hong Seok Choi
Keyword(s):  
Breast Cancer ◽  
Epithelial Cell ◽  
Cell Transformation ◽  
Mouse Skin ◽  
Breast Tumorigenesis ◽  
Mcf7 Cells ◽  
Cellular Processes ◽  
Signaling Axis ◽  
4T1 Cells

IL-34 has been recently identified as a ligand for CSF1R that regulates various cellular processes including cell proliferation, survival, and differentiation. Although the binding of IL-34 to CSF1R modulates several cancer-driving signaling pathways, little is known about the role of IL-34/CSF1R signaling in breast cancer. Herein, we report that IL-34 induces epithelial cell transformation and breast tumorigenesis through activation of MEK/ERK and JNK/c-Jun pathways. IL-34 increased the phosphorylation of MEK1/2, ERK1/2, JNK1/2, and c-Jun through CSF1R in mouse skin epidermal JB6 C141 cells and human breast cancer MCF7 cells. IL-34 enhanced c-Fos and c-Jun promoter activity, resulting in increased AP-1 transactivation activity in JB6 Cl41 and MCF7 cells. Moreover, PIN1 enhanced IL-34-induced phosphorylation of MEK1/2, ERK1/2, JNK1/2, and c-Jun in JB6 Cl41 and MCF7 cells. Inhibition of PIN1 using juglone prevented the IL-34-induced transformation of JB6 C141 cells. Similarly, silencing of PIN1 reduced the IL-34-induced tumorigenicity of MCF7 cells. Consistent with these results, the synergistic model showed that treatment with juglone suppressed the IL-34-induced growth of tumors formed by 4T1 cells in BALB/c mice. Our study demonstrates the role of IL-34-induced MEK/ERK and JNK/c-Jun cascades in breast cancer and highlights the regulatory role of PIN1 in IL-34-induced breast tumorigenesis.

Sign in / Sign up

Export Citation Format

Share Document