scholarly journals The functional role of long noncoding RNA in resistance to anticancer treatment

2020 ◽  
Vol 12 ◽  
pp. 175883592092785
Author(s):  
Yidi Qu ◽  
Hor-Yue Tan ◽  
Yau-Tuen Chan ◽  
Hongbo Jiang ◽  
Ning Wang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Drug Efflux ◽  
Mechanisms Of Resistance ◽  
Mesenchymal Transition ◽  
Damage Repair ◽  
Different Types ◽  
Anticancer Treatment

Chemotherapy is one of the fundamental methods of cancer treatment. However, drug resistance remains the main cause of clinical treatment failure. We comprehensively review the newly identified roles of long noncoding RNAs (lncRNAs) in oncobiology that are associated with drug resistance. The expression of lncRNAs is tissue-specific and often dysregulated in human cancers. Accumulating evidence suggests that lncRNAs are involved in chemoresistance of cancer cells. The main lncRNA-driven mechanisms of chemoresistance include regulation of drug efflux, DNA damage repair, cell cycle, apoptosis, epithelial-mesenchymal transition (EMT), induction of signaling pathways, and angiogenesis. LncRNA-driven mechanisms of resistance to various antineoplastic agents have been studied extensively. There are unique mechanisms of resistance against different types of drugs, and each mechanism may have more than one contributing factor. We summarize the emerging strategies that can be used to overcome the technical challenges in studying and addressing lncRNA-mediated drug resistance.

scholarly journals Long Noncoding RNA and Epithelial Mesenchymal Transition in Cancer

2019 ◽  
Vol 20 (8) ◽  
pp. 1924 ◽  
Author(s):  
Gugnoni ◽  
Ciarrocchi
Keyword(s):  
Cancer Biology ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Protein Localization ◽  
Noncoding Rnas ◽  
Therapeutic Targets ◽  
Mesenchymal Transition ◽  
Multistep Process ◽  
Genomic Studies

Epithelial–mesenchymal transition (EMT) is a multistep process that allows epithelial cells to acquire mesenchymal properties. Fundamental in the early stages of embryonic development, this process is aberrantly activated in aggressive cancerous cells to gain motility and invasion capacity, thus promoting metastatic phenotypes. For this reason, EMT is a central topic in cancer research and its regulation by a plethora of mechanisms has been reported. Recently, genomic sequencing and functional genomic studies deepened our knowledge on the fundamental regulatory role of noncoding DNA. A large part of the genome is transcribed in an impressive number of noncoding RNAs. Among these, long noncoding RNAs (lncRNAs) have been reported to control several biological processes affecting gene expression at multiple levels from transcription to protein localization and stability. Up to now, more than 8000 lncRNAs were discovered as selectively expressed in cancer cells. Their elevated number and high expression specificity candidate these molecules as a valuable source of biomarkers and potential therapeutic targets. Rising evidence currently highlights a relevant function of lncRNAs on EMT regulation defining a new layer of involvement of these molecules in cancer biology. In this review we aim to summarize the findings on the role of lncRNAs on EMT regulation and to discuss their prospective potential value as biomarkers and therapeutic targets in cancer.

scholarly journals Snail-Family Proteins: Role in Carcinogenesis and Prospects for Antitumor Therapy

Acta Naturae ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 76-90
Author(s):  
Margarita A. Yastrebova ◽  
Alvina I. Khamidullina ◽  
Victor V. Tatarskiy ◽  
Alexander M. Scherbakov
Keyword(s):  
Cancer Biology ◽  
Epithelial Mesenchymal Transition ◽  
Chemical Compounds ◽  
Post Translational Modification ◽  
Mesenchymal Transition ◽  
Signaling Mechanisms ◽  
Snail Family ◽  
Anticancer Treatment ◽  
Snail Proteins

The review analyzes Snail family proteins, which are transcription factors involved in the regulation of the epithelial-mesenchymal transition (EMT) of tumor cells. We describe the structure of these proteins, their post-translational modification, and the mechanisms of Snail-dependent regulation of genes. The role of Snail proteins in carcinogenesis, invasion, and metastasis is analyzed. Furthermore, we focus on EMT signaling mechanisms involving Snail proteins. Next, we dissect Snail signaling in hypoxia, a condition that complicates anticancer treatment. Finally, we offer classes of chemical compounds capable of down-regulating the transcriptional activity of Snails. Given the important role of Snail proteins in cancer biology and the potential for pharmacological inhibition, Snail family proteins may be considered promising as therapeutic targets.

Epithelial-mesenchymal transition and H2O2 signaling – a driver of disease progression and a vulnerability in cancers

2022 ◽  
Vol 0 (0) ◽  
Author(s):  
Anna V. Milton ◽  
David B. Konrad
Keyword(s):  
Quality Of Life ◽  
Overall Survival ◽  
Drug Resistance ◽  
Disease Progression ◽  
Posttranslational Modifications ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Anticancer Treatment

Abstract Mutation-selective drugs constitute a great advancement in personalized anticancer treatment with increased quality of life and overall survival in cancers. However, the high adaptability and evasiveness of cancers can lead to disease progression and the development of drug resistance, which cause recurrence and metastasis. A common characteristic in advanced neoplastic cancers is the epithelial-mesenchymal transition (EMT) which is strongly interconnected with H2O2 signaling, increased motility and invasiveness. H2O2 relays its signal through the installation of oxidative posttranslational modifications on cysteines. The increased H2O2 levels that are associated with an EMT confer a heightened sensitivity towards the induction of ferroptosis as a recently discovered vulnerability.

scholarly journals Role of ACTN4 in Tumorigenesis, Metastasis, and EMT

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1427 ◽  
Author(s):  
Dmitri Tentler ◽  
Ekaterina Lomert ◽  
Ksenia Novitskaya ◽  
Nikolai A. Barlev
Keyword(s):  
Chromosomal Region ◽  
Epithelial Mesenchymal Transition ◽  
Research Progress ◽  
Actin Binding ◽  
Mesenchymal Transition ◽  
Functional Studies ◽  
Cytoskeleton Reorganization ◽  
Different Types ◽  
Nuclear Processes

The actin-binding protein ACTN4 belongs to a family of actin-binding proteins and is a non-muscle alpha-actinin that has long been associated with cancer development. Numerous clinical studies showed that changes in ACTN4 gene expression are correlated with aggressiveness, invasion, and metastasis in certain tumors. Amplification of the 19q chromosomal region where the gene is located has also been reported. Experimental manipulations with ACTN4 expression further confirmed its involvement in cell proliferation, motility, and epithelial-mesenchymal transition (EMT). However, both clinical and experimental data suggest that the effects of ACTN4 up- or down-regulation may vary a lot between different types of tumors. Functional studies demonstrated its engagement in a number of cytoplasmic and nuclear processes, ranging from cytoskeleton reorganization to regulation of different signaling pathways. Such a variety of functions may be the reason behind cell type and cell line specific responses. Herein, we will review research progress and controversies regarding the prognostic and functional significance of ACTN4 for tumorigenesis.

scholarly journals The role of epithelial–mesenchymal transition-regulating transcription factors in anti-cancer drug resistance

2021 ◽  
Author(s):  
Jihye Seo ◽  
Jain Ha ◽  
Eunjeong Kang ◽  
Sayeon Cho
Keyword(s):  
Drug Resistance ◽  
Transcription Factors ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Drug ◽  
Preclinical Studies ◽  
Mesenchymal Transition ◽  
Cancer Drug Resistance ◽  
Anti Cancer ◽  
Future Challenges

AbstractThe complex orchestration of gene expression that mediates the transition of epithelial cells into mesenchymal cells is implicated in cancer development and metastasis. As the primary regulator of the process, epithelial-mesenchymal transition-regulating transcription factors (EMT-TFs) play key roles in metastasis. They are also highlighted in recent preclinical studies on resistance to cancer therapy. This review describes the role of three main EMT-TFs, including Snail, Twist1, and zinc-finger E homeobox-binding 1 (ZEB1), relating to drug resistance and current possible approaches for future challenges targeting EMT-TFs.

scholarly journals Mechanistic Insights Delineating the Role of Cholesterol in Epithelial Mesenchymal Transition and Drug Resistance in Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Naaziyah Abdulla ◽  
C. Theresa Vincent ◽  
Mandeep Kaur
Keyword(s):  
Drug Resistance ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Cholesterol Metabolism ◽  
Cholesterol Content ◽  
Multi Drug Resistance ◽  
Mesenchymal Transition ◽  
Proposed Model

Despite the significant advancements made in targeted anti-cancer therapy, drug resistance constitutes a multifaceted phenomenon leading to therapy failure and ultimately mortality. Emerging experimental evidence highlight a role of cholesterol metabolism in facilitating drug resistance in cancer. This review aims to describe the role of cholesterol in facilitating multi-drug resistance in cancer. We focus on specific signaling pathways that contribute to drug resistance and the link between these pathways and cholesterol. Additionally, we briefly discuss the molecular mechanisms related to the epithelial-mesenchymal transition (EMT), and the documented link between EMT, metastasis and drug resistance. We illustrate this by specifically focusing on hypoxia and the role it plays in influencing cellular cholesterol content following EMT induction. Finally, we provide a proposed model delineating the crucial role of cholesterol in EMT and discuss whether targeting cholesterol could serve as a novel means of combatting drug resistance in cancer progression and metastasis.

Downregulation of long noncoding RNA T1NCR inhibits cell proliferation, invasion, and epithelial-mesenchymal transition of hepatocellular carcinoma

2021 ◽  
Vol 7 (6) ◽  
pp. 6499-6510
Author(s):  
Hongjuan Li ◽  
Yaqin Chen ◽  
Chunyan Wu ◽  
Haiyan Zhao ◽  
Xuesong Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Normal Tissues ◽  
Proliferation Ability ◽  
Non Coding Rnas

Accumulating reports have identified that long non-coding RNAs (IncRNAs) function as key regulators of tumor initiation and progression. The aim of the current study was to determine the clinical significance and functional role of TINCR in hepatocellular carcinoma (HCC). In the present study, the level of IncRNA TINCR expression was significantly upregulated in HCC tissues compared to adjacent normal tissues. Higher levels of IncRNA TINCR expression were significantly correlated with tumor size and vascular invasion of HCC patients. LncRNA TINCR knockdown inhibited cell proliferation ability, increased the proportion of G1 phase cells, reduced the proportion of S phase cells, and suppressed cell invasion of HCC in vitro. Additionally, IncRNA TINCR knockdown inhibited the HCC cell epithelial-mesenchymal transition (EMT) phenomenon by upregulating E-cadherin and reducing N-cadherin expression. We demonstrated that knockdown of IncRNA reduced tumor growth in vivo. Thus, these results indicated that IncRNA TINCR exhibits a tumor oncogenic role in HCC and inhibition of IncRNA TINCR might serve as a therapeutic target for HCC.

Secretory Clusterin: A Promising Target for Chemoresistance of Hepatocellular Carcinoma

2020 ◽  
Vol 20 (12) ◽  
pp. 1153-1165 ◽  
Author(s):  
Jie Zhang ◽  
Mengna Wu ◽  
Yuqing Xu ◽  
Qianqian Song ◽  
Wenjie Zheng
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Resistance ◽  
Epithelial Mesenchymal Transition ◽  
Vital Role ◽  
Current Evidence ◽  
Drug Efflux ◽  
Mesenchymal Transition ◽  
Limited Efficacy ◽  
Promising Target ◽  
Chemotherapy Agents

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. Chemoresistance remains the major factor for limited efficacy of the HCC treatment. Thus, exploring the mechanisms underlying drug resistance is of great importance. Secretory clusterin (sCLU), a stressactivated and ATP-independent molecular chaperone, is up-regulated in numerous tumors and correlated with malignant phenotypes. For HCC, the implication of sCLU was previously addressed in tumor growth, metastasis, as well as early diagnosis and poor prognosis. Notably, accumulating studies have emphasized its vital role in drug resistance of HCC. Depletion of sCLU synergistically could enhance the sensitivity of HCC cells to a variety of chemotherapy agents. Herein, we summarized the potential mechanisms accounting for the sCLU-induced chemoresistance, including promoting apoptosis evasion, facilitating epithelial-mesenchymal transition (EMT), maintaining the viability of cancer stem cell (CSC), enhancing drug efflux capacity, and regulating autophagic activities. The current evidence suggest that targeting sCLU might be a promising approach in overcoming chemoresistance of HCC.

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