scholarly journals Regulation of GSTu1-mediated insecticide resistance in Plutella xylostella by miRNA and lncRNA

PLoS Genetics ◽  
2021 ◽  
Vol 17 (10) ◽  
pp. e1009888
Author(s):  
Bin Zhu ◽  
Linhong Li ◽  
Rui Wei ◽  
Pei Liang ◽  
Xiwu Gao
Keyword(s):  
Drug Resistance ◽  
Insecticide Resistance ◽  
Plutella Xylostella ◽  
Mrna Stability ◽  
Noncoding Rna ◽  
Antisense Transcript ◽  
Regulatory Mechanisms ◽  
Detoxifying Enzymes ◽  
Evolution Of Resistance

The evolution of resistance to insecticides is well known to be closely associated with the overexpression of detoxifying enzymes. Although the role of glutathione S-transferase (GST) genes in insecticide resistance has been widely reported, the underlying regulatory mechanisms are poorly understood. Here, one GST gene (GSTu1) and its antisense transcript (lnc-GSTu1-AS) were identified and cloned, and both of them were upregulated in several chlorantraniliprole-resistant Plutella xylostella populations. GSTu1 was confirmed to be involved in chlorantraniliprole resistance by direct degradation of this insecticide. Furthermore, we demonstrated that lnc-GSTu1-AS interacted with GSTu1 by forming an RNA duplex, which masked the binding site of miR-8525-5p at the GSTu1-3′UTR. In summary, we revealed that lnc-GSTu1-AS maintained the mRNA stability of GSTu1 by preventing its degradation that could have been induced by miR-8525-5p and thus increased the resistance of P. xylostella to chlorantraniliprole. Our findings reveal a new noncoding RNA-mediated pathway that regulates the expression of detoxifying enzymes in insecticide-resistant insects and offer opportunities for the further understanding of the mechanisms of insecticide and drug resistance.

scholarly journals RAC1 Takes the Lead in Solid Tumors

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 382 ◽  
Author(s):  
Pradip De ◽  
Jennifer Carlson Aske ◽  
Nandini Dey
Keyword(s):  
Drug Resistance ◽  
Embryonic Development ◽  
Solid Tumors ◽  
Tumor Cells ◽  
Cellular Localization ◽  
Regulatory Mechanisms ◽  
Cellular Functions ◽  
Patterns Of Distribution ◽  
Background Data

Three GTPases, RAC, RHO, and Cdc42, play essential roles in coordinating many cellular functions during embryonic development, both in healthy cells and in disease conditions like cancers. We have presented patterns of distribution of the frequency of RAC1-alteration(s) in cancers as obtained from cBioPortal. With this background data, we have interrogated the various functions of RAC1 in tumors, including proliferation, metastasis-associated phenotypes, and drug-resistance with a special emphasis on solid tumors in adults. We have reviewed the activation and regulation of RAC1 functions on the basis of its sub-cellular localization in tumor cells. Our review focuses on the role of RAC1 in cancers and summarizes the regulatory mechanisms, inhibitory efficacy, and the anticancer potential of RAC1-PAK targeting agents.

scholarly journals Mitophagy in carcinogenesis, drug resistance and anticancer therapeutics

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yanjie Guan ◽  
Yifei Wang ◽  
Bo Li ◽  
Kai Shen ◽  
Quanfu Li ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Energy Production ◽  
Cellular Differentiation ◽  
Vital Role ◽  
Regulatory Mechanisms ◽  
Physiological Processes ◽  
Promising Strategy ◽  
New Frontier ◽  
Anticancer Therapeutics

AbstractThe mitochondrion is an organelle that plays a vital role in energy production, cytoplasmic protein degradation and cell death. Mitophagy is an autophagic procedure that specifically clears damaged mitochondria and maintains its homeostasis. Emerging evidence indicates that mitophagy is involved in many physiological processes, including cellular homeostasis, cellular differentiation and nerve protection. In this review, we describe the regulatory mechanisms of mitophagy in mammals and yeasts and highlight the recent advances relevant to its function in carcinogenesis and drug resistance. Finally, a section has been dedicated to describing the role of mitophagy in anticancer therapeutics, which is a new frontier that offers a precise and promising strategy.

scholarly journals Reduced Expression of a Novel Midgut Trypsin Gene Involved in Protoxin Activation Correlates with Cry1Ac Resistance in a Laboratory-Selected Strain of Plutella xylostella (L.)

Toxins ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 76 ◽  
Author(s):  
Lijun Gong ◽  
Shi Kang ◽  
Junlei Zhou ◽  
Dan Sun ◽  
Le Guo ◽  
...  
Keyword(s):  
Plutella Xylostella ◽  
Insect Pests ◽  
Sustainable Use ◽  
High Dose ◽  
Protease Gene ◽  
Rna Seq ◽  
Down Regulation ◽  
Bt Toxins ◽  
Evolution Of Resistance

Bacillus thuringiensis (Bt) produce diverse insecticidal proteins to kill insect pests. Nevertheless, evolution of resistance to Bt toxins hampers the sustainable use of this technology. Previously, we identified down-regulation of a trypsin-like serine protease gene PxTryp_SPc1 in the midgut transcriptome and RNA-Seq data of a laboratory-selected Cry1Ac-resistant Plutella xylostella strain, SZ-R. We show here that reduced PxTryp_SPc1 expression significantly reduced caseinolytic and trypsin protease activities affecting Cry1Ac protoxin activation, thereby conferring higher resistance to Cry1Ac protoxin than activated toxin in SZ-R strain. Herein, the full-length cDNA sequence of PxTryp_SPc1 gene was cloned, and we found that it was mainly expressed in midgut tissue in all larval instars. Subsequently, we confirmed that the PxTryp_SPc1 gene was significantly decreased in SZ-R larval midgut and was further reduced when selected with high dose of Cry1Ac protoxin. Moreover, down-regulation of the PxTryp_SPc1 gene was genetically linked to resistance to Cry1Ac in the SZ-R strain. Finally, RNAi-mediated silencing of PxTryp_SPc1 gene expression decreased larval susceptibility to Cry1Ac protoxin in the susceptible DBM1Ac-S strain, supporting that low expression of PxTryp_SPc1 gene is involved in Cry1Ac resistance in P. xylostella. These findings contribute to understanding the role of midgut proteases in the mechanisms underlying insect resistance to Bt toxins.

scholarly journals Role of noncoding RNA in drug resistance of prostate cancer

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Lifeng Ding ◽  
Ruyue Wang ◽  
Danyang Shen ◽  
Sheng Cheng ◽  
Huan Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Drug Resistance ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Vital Role ◽  
Cellular Processes ◽  
Non Coding Rna ◽  
Remarkable Progress ◽  
Made In

AbstractProstate cancer is one of the most prevalent forms of cancer around the world. Androgen-deprivation treatment and chemotherapy are the curative approaches used to suppress prostate cancer progression. However, drug resistance is extensively and hard to overcome even though remarkable progress has been made in recent decades. Noncoding RNAs, such as miRNAs, lncRNAs, and circRNAs, are a group of cellular RNAs which participate in various cellular processes and diseases. Recently, accumulating evidence has highlighted the vital role of non-coding RNA in the development of drug resistance in prostate cancer. In this review, we summarize the important roles of these three classes of noncoding RNA in drug resistance and the potential therapeutic applications in this disease.

Resistance to platinum-based cancer drugs: a special focus on epigenetic mechanisms

2021 ◽  
Author(s):  
Yuselin Mora ◽  
María Elena Reyes ◽  
Louise Zanella ◽  
Bárbara Mora ◽  
Kurt Buchegger ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Noncoding Rna ◽  
Drug Response ◽  
Epigenetic Therapy ◽  
Special Focus ◽  
Epigenetic Mechanisms ◽  
Platinum Drug ◽  
Expression Of Genes ◽  
Potential Synergy

Chemoresistance is a significant clinical challenge, limiting the drug response in cancer. Several mechanisms associated with drug resistance have been characterized, and the role of epigenetics in generating resistance to platinum-based drugs has been clarified. Epigenetic mechanisms such as DNA methylation, histone modification, long noncoding RNA, and microRNA affect the expression of genes implicated in absorption, distribution, metabolism and excretion (ADME) of drugs, and other non-ADME genes that encode enzymes involved in the processes of cell proliferation, DNA repair, apoptosis and signal transduction key in the development of chemoresistance in cancer, specifically in platinum-based drugs. This review summarizes current discoveries in epigenetic regulation implicated in platinum drug resistance in cancer and the main clinical trials based on epigenetic therapy, evaluating their potential synergy with platinum-based drugs.

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.

Methods to unravel the role of HDAC10 in autophagy-related drug resistance

2015 ◽  
Vol 227 (06/07) ◽  
Author(s):  
J Fabian ◽  
J Ridinger ◽  
O Witt ◽  
I Oehme
Keyword(s):  
Drug Resistance ◽  
Related Drug
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