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https://www.readbyqxmd.com/read/28921648/rna-therapeutics-in-oncology-advances-challenges-and-future-directions
#1
A Robert MacLeod, Stanley T Crooke
RNA-based therapeutic technologies represent a rapidly expanding class of therapeutic opportunities with the power to modulate cellular biology in ways never before possible. With RNA-targeted therapeutics, inhibitors of previously undruggable proteins, gene expression modulators, and even therapeutic proteins can be rationally designed based on sequence information alone, something that is not possible with other therapeutic modalities. The most advanced RNA therapeutic modalities are antisense oligonucleotides (ASOs) and small interfering RNAs...
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28914367/no-association-of-single-nucleotide-polymorphisms-within-h19-and-hox-transcript-antisense-rna-hotair-with-genetic-susceptibility-to-systemic-lupus-erythematosus-rheumatoid-arthritis-and-primary-sj%C3%A3-gren-s-syndrome-in-a-chinese-han-population
#2
An-Fang Huang, Lin-Chong Su, Hong Jia, Yi Liu, Wang-Dong Xu
The H19 (rs2839698, rs3741219) and HOTAIR (rs920778) polymorphisms were related to many kinds of cancers. However, these polymorphisms have been scarcely explored in different autoimmune diseases. Here, we aimed to examine the association of the polymorphisms with susceptibility to or protection against systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sjögren's syndrome (pSS) among Chinese Han patients. We conducted a case-control study including 800 patients (300 with SLE, 350 with RA, and 150 with pSS) and 350 healthy control individuals...
September 15, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28911087/an-antisense-oligonucleotide-targeting-tgf-%C3%AE-2-inhibits-lung-metastasis-and-induces-cd86-expression-in-tumor-associated-macrophages
#3
I Huber-Ruano, C Raventós, I Cuartas, C Sánchez-Jaro, A Arias, J L Parra, K Wosikowski, M Janicot, J Seoane
Background: The transforming growth factor (TGF)-β pathway is a well-described inducer of immunosuppression and can act as an oncogenic factor in advanced tumors. Several preclinical and clinical studies show that the TGF-β pathway can be considered a promising molecular target for cancer therapy. The human genome has three TGF-β isoforms and not much is known about the oncogenic response to each of the isoforms. Here, we studied the antitumor response to ISTH0047, a recently developed locked nucleic acid-modified antisense oligonucleotide targeting TGF-β2...
September 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28904332/identification-of-sites-of-2-o-methylation-vulnerability-in-human-ribosomal-rnas-by-systematic-mapping
#4
Sunny Sharma, Virginie Marchand, Yuri Motorin, Denis L J Lafontaine
Ribosomal RNA modifications are important in optimizing ribosome function. Sugar 2'-O-methylation performed by fibrillarin-associated box C/D antisense guide snoRNAs impacts all steps of translation, playing a role in disease etiology (cancer). As it renders adjacent phosphodiester bonds resistant to alkaline treatment, 2'-O-methylation can be monitored qualitatively and quantitatively by applying next-generation sequencing to fragments of randomly cleaved RNA. We remapped all sites of 2'-O-methylation in human rRNAs in two isogenic diploid cell lines, one producing and one not producing the antitumor protein p53...
September 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28901461/mir106b-regulates-retinoblastoma-y79-cells-through-runx3
#5
Ge Yang, Yang Fu, Luxi Zhang, Xiaoyan Lu, Qiuming Li
MicroRNAs are increasingly recognized as important regulators of cancer. The aim of the present study was to investigate the role of miR-106b in the regulation of Y79 retinoblastoma. Y79 cells were transfected with antisense oligonucleotides (ASO) against miR-106b (ASO-miR-106b) or ASO-control. After transfection, the levels of miR-106b were monitored with real-time PCR (RT-PCR). The effects of ASO-miR-106b transfection on cell viability was evaluated by Cell Counting Kit-8 (CCK-8) analysis at 24, 48 and 72 h after transfection...
August 30, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28894380/lef1-as1-a-long-noncoding-rna-promotes-malignancy-in-glioblastoma
#6
Jin Wang, Xiaoyang Liu, Changsheng Yan, Jie Liu, Songtao Wang, Yongzhi Hong, Aihua Gu, Peng Zhao
OBJECTIVES: The long-noncoding RNAs (lncRNAs) are identified as new crucial regulators of diverse cellular processes in glioblastoma (GBM) tissues. However, the expression pattern and biological function of lncRNAs remain largely unknown. Here, for the first time, the effects of lncRNA lymphoid enhancer-binding factor 1 antisense RNA 1 (LEF1-AS1) on GBM progression both in vitro and in vivo are investigated. MATERIALS AND METHODS: Expression profiles of LEF1-AS1 in GBM specimens were investigated by bioinformatics analyses...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28892615/quantitative-proteomics-reveals-the-regulatory-networks-of-circular-rna-cdr1as-in-hepatocellular-carcinoma-cells
#7
Yang Xue, Qian Xiong, Ying Wu, Siting Li, Feng Ge
Circular RNAs (circRNAs), a class of widespread endogenous RNAs, play crucial roles in diverse biological processes and are potential biomarkers in diverse human diseases and cancers. Cerebellar degeneration-related protein 1 antisense RNA (CDR1as), an oncogenic circRNA, is involved in human tumorigenesis and is dysregulated in hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying CDR1as functions in HCC remain unclear. Here, we explored the functions of CDR1as and searched for CDR1as-regulated proteins in HCC cells...
September 11, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28886528/an-increased-expression-of-long-non-coding-rna-pandar-promotes-cell-proliferation-and-inhibits-cell-apoptosis-in-pancreatic-ductal-adenocarcinoma
#8
Yuehong Jiang, Enhang Feng, Lifang Sun, Wei Jin, Yuhong You, Yue Yao, Yi Xu
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies worldwide. Emerging evidence indicates that aberrantly expressed long non-coding RNAs (lncRNAs) act as imperative roles in tumorigenesis and progression. PANDAR (promoter of CDKN1A antisense DNA damage activated RNA) is a novel lncRNA that contributes to the development of various cancers. However, its clinical significance and potential effects on PDAC remains unknown. In the present study, qRT-PCR was performed to explore the expression levels of PANDAR in PDAC tissues and corresponding non-tumor tissues, the correlation between PANDAR expression and clinicopathological characteristics was also analyzed...
September 5, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28873379/a-novel-long-non-coding-rna-sox21-as1-indicates-a-poor-prognosis-and-promotes-lung-adenocarcinoma-proliferation
#9
Xiyi Lu, Chenjun Huang, Xuezhi He, Xinyin Liu, Jianmei Ji, Erbao Zhang, Wei Wang, Renhua Guo
BACKGROUND: In recent years, long non-coding RNAs (lncRNAs) have been shown to be a novel class of regulators of cancer biological processes. Although lncRNAs are dysregulated in numerous cancer types, limited data are available on the expression profiles and potential functions of lncRNAs in lung adenocarcinoma (LUAD). This study evaluated the expression and biological roles of lncRNA SOX21 antisense RNA 1 (SOX21-AS1) in LUAD. METHODS: Quantitative reverse transcription PCR (qRT-PCR) was performed to detect the expression levels of SOX21-AS1 in 68 pairs of LUAD tissues and corresponding non-tumor tissues...
July 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28866730/egfr-targeted-therapies-in-the-post-genomic-era
#10
Mary Jue Xu, Daniel E Johnson, Jennifer R Grandis
Over 90% of head and neck cancers overexpress the epidermal growth factor receptor (EGFR). In diverse tumor types, EGFR overexpression has been associated with poorer prognosis and outcomes. Therapies targeting EGFR include monoclonal antibodies, tyrosine kinase inhibitors, phosphatidylinositol 3-kinase (PI3K) inhibitors, and antisense gene therapy. Few EGFR-targeted therapeutics are approved for clinical use. The monoclonal antibody cetuximab is a Food and Drug Administration (FDA)-approved EGFR-targeted therapy, yet has exhibited modest benefit in clinical trials...
September 2, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28839185/antisense-oligonucleotide-and-thyroid-hormone-conjugates-for-obesity-treatment
#11
Yang Cao, Tomoko Matsubara, Can Zhao, Wei Gao, Linxiu Peng, Jinjun Shan, Zhengxia Liu, Fang Yuan, Lingyi Tang, Peixin Li, Zhibin Guan, Zhuyuan Fang, Xiang Lu, Hu Huang, Qin Yang
Using the principle of antibody-drug conjugates that deliver highly potent cytotoxic agents to cancer cells for cancer therapy, we here report the synthesis of antisense-oligonucleotides (ASO) and thyroid hormone T3 conjugates for obesity treatment. ASOs primarily target fat and liver with poor penetrance to other organs. Pharmacological T3 treatment increases energy expenditure and causes weight loss, but is contraindicated for obesity treatment due to systemic effects on multiple organs. We hypothesize that ASO-T3 conjugates may knock down target genes and enrich T3 action in fat and liver...
August 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28832537/high-boron-loaded-dna-oligomers-as-potential-boron-neutron-capture-therapy-and-antisense-oligonucleotide-dual-action-anticancer-agents
#12
Damian Kaniowski, Katarzyna Ebenryter-Olbińska, Milena Sobczak, Błażej Wojtczak, Sławomir Janczak, Zbigniew J Leśnikowski, Barbara Nawrot
Boron cluster-modified therapeutic nucleic acids with improved properties are of interest in gene therapy and in cancer boron neutron capture therapy (BNCT). High metallacarborane-loaded antisense oligonucleotides (ASOs) targeting epidermal growth factor receptor (EGFR) were synthesized through post-synthetic Cu (I)-assisted "click" conjugation of alkyne-modified DNA-oligonucleotides with a boron cluster alkyl azide component. The obtained oligomers exhibited increased lipophilicity compared to their non-modified precursors, while their binding affinity to complementary DNA and RNA strands was slightly decreased...
August 23, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28832185/long-noncoding-rna-hoxa11-as-functions-as-mirna-sponge-to-promote-the-glioma-tumorigenesis-through-targeting-mir-140-5p
#13
Yan Cui, Lei Yi, Ji-Zong Zhao, Yu-Gang Jiang
Long noncoding RNAs (lncRNAs) have been proved as important regulators in many diseases, including cancers. HOXA11 antisense RNA (HOXA11-AS) is a novel identified lncRNA associated with cancer progression. However, the role of HOXA11-AS in glioma remains poorly understood and needs to be elucidated. The purpose of this study is to investigate the role and regulating mechanism of HOXA11-AS on gliomagenesis. Expression of HOXA11-AS was significantly upregulated in glioma tissue and cell lines compared with the adjacent normal tissue and cells...
August 23, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28830551/long-noncoding-rna-zeb1-as1-epigenetically-regulates-the-expressions-of-zeb1-and-downstream-molecules-in-prostate-cancer
#14
Wenjing Su, Miao Xu, Xueqin Chen, Ni Chen, Jing Gong, Ling Nie, Ling Li, Xinglan Li, Mengni Zhang, Qiao Zhou
BACKGROUND: Emerging studies show that long noncoding RNAs (lncRNAs) play important roles in carcinogenesis and cancer progression. The lncRNA ZEB1 antisense 1 (ZEB1-AS1) derives from the promoter region of ZEB1 and we still know little about its expressions, roles and mechanisms. METHODS: RACE was used to obtain the sequence of ZEB1-AS1. RNA interference was used to decrease ZEB1-AS1 expression. Adenovirus expression vector was used to increase ZEB1-AS1 expression...
August 23, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28805496/natural-antisense-transcripts-drive-a-regulatory-cascade-controlling-c-myc-transcription
#15
Sara Napoli, Valentina Piccinelli, Sarah Mapelli, Giuseppina Pisignano, Carlo V Catapano
Cis-natural antisense transcripts (cis-NATs) are long noncoding RNAs transcribed from the opposite strand and overlapping coding and noncoding genes on the sense strand. cis-NATs are widely present in the human genome and can be involved in multiple mechanisms of gene regulation. Here, we describe the presence of cis-NATs in the 3' distal region of the c-MYC locus and investigate their impact on transcriptional regulation of this key oncogene in human cancers. We found that cis-NATs are produced as consequence of the activation of cryptic transcription initiation sites in the 3' distal region downstream of the c-MYC 3'UTR...
August 14, 2017: RNA Biology
https://www.readbyqxmd.com/read/28803245/mir-143-5p-deficiency-triggers-emt-and-metastasis-by-targeting-hif-1%C3%AE-in-gallbladder-cancer
#16
Min He, Ming Zhan, Wei Chen, Sunwang Xu, Manmei Long, Hui Shen, Yongheng Shi, Qiang Liu, Man Mohan, Jian Wang
BACKGROUND/AIMS: Early metastasis plays a pivotal role in tumor-caused death in gallbladder cancer (GBC) patients. Increasing evidence suggest that miR-143-5p is an active player involved in cancer metastasis and a potential therapeutic target. However, its role in the development of GBC cells remains unclear. The aim of this study is to reveal the inhibiting effects of miR-143-5p on the proliferation and metastasis in GBC. METHODS: Quantitative real-time PCR were used to investigate miR-143-5p and its target HIF-1α mRNA levels...
August 11, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28791413/knockdown-of-hotair-suppresses-proliferation-and-cell-cycle-progression-in-hepatocellular-carcinoma-cell-by-downregulating-ccnd1-expression
#17
Jia-Jia Zhou, Di Cheng, Xiao-Yu He, Zhe Meng, Wen-Zhu Li, Ru-Fu Chen
The long noncoding RNA, homeobox transcript antisense RNA (Hotair), has been demonstrated to have an important role in regulating various biological processes in various cancers, including hepatocellular carcinoma (HCC). However, the importance of Hotair in HCC proliferation and cell cycle progression remains to be elucidated. In the present study, knockdown of HOTAIR expression by RNA interference inhibited cell proliferation and induced G0/G1 cell cycle arrest in Huh7 hepatocellular carcinoma cells. In addition, the expression levels of CCND1 mRNA and its cyclin D1 protein product were reduced in Huh7 cells following knockdown of HOTAIR...
October 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28791380/knockdown-of-lncrna-hnf1a-as1-inhibits-oncogenic-phenotypes-in-colorectal-carcinoma
#18
Wenyi Zhu, Peipei Zhuang, Wen Song, Shiyu Duan, Qiong Xu, Man Peng, Jun Zhou
Long non-coding RNAs (lncRNAs) have been demonstrated to serve important roles in the development and progression of cancer. Recently HNF1A antisense RNA 1 (HNF1A‑AS1), a lncRNA, has been reported as exhibiting a potential oncogenic role in the development of many types of cancer. However, the expression and the role of HNF1A‑AS1 in colorectal carcinoma (CRC) remains unclear. In the present study, the role of HNF1A‑AS1 in CRC was examined for the first time and its correlation with CRC cell biological behaviors was analyzed...
October 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28790838/downregulation-of-lncrna-sdpr-as-is-associated-with-poor-prognosis-in-renal-cell-carcinoma
#19
Wenjun Ni, Erlin Song, Mancheng Gong, Yongxiang Li, Jie Yao, Ruihua An
Renal cell carcinoma (RCC) is a common type of kidney cancer. Normally, surgical treatment can prolong life, but only for patients with early stage tumors. However, it is difficult for early detection strategies to distinguish between benign and malignant kidney tumors. Therefore, potential biomarkers for early diagnosis and prognosis of RCC are needed. Intriguingly, mounting evidence has demonstrated that many long noncoding RNAs (lncRNAs) are strongly linked to cancers. Indeed, promising RCC-associated lncRNA biomarkers have also been identified...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28782835/identification-and-functional-analysis-of-a-potential-key-lncrna-involved-in-fat-loss-of-cancer-cachexia
#20
Huiquan Liu, Ting Zhou, Bangyan Wang, Lu Li, Dawei Ye, Shiying Yu
Cancer cachexia is a devastating, multifactorial, and irreversible syndrome characterized by skeletal muscle reduction with or without fat loss. Although much attention has been focused on muscle wasting, fat loss may occur earlier and accelerate muscle wasting in cachexia. The cause of 20% of cancer related death makes it urgent to discover molecular mechanisms behind cancer cachexia. Here we applied weighted gene co-expression network analysis (WGCNA) to identify cachexia related gene modules using differentially expressed 3289 genes and 59 long non-coding RNAs based on microarray data of cachectic and non-cachectic subcutaneous adipose tissue...
August 7, 2017: Journal of Cellular Biochemistry
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