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Item Aberrant Expression Profiles of lncRNAs and Their Associated Nearby Coding Genes in the Hippocampus of the SAMP8 Mouse Model with AD(Cell Press, 2020-06-05) Hong, Honghai; Mo, Yousheng; Li, Dongli; Xu, Zhiheng; Liao, Yanfang; Yin, Ping; Liu, Xinning; Xia, Yong; Fang, Jiansong; Wang, Qi; Fang, Shuhuan; Pathology and Laboratory Medicine, School of MedicineThe senescence-accelerated mouse prone 8 (SAMP8) mouse model is a useful model for investigating the fundamental mechanisms involved in the age-related learning and memory deficits of Alzheimer's disease (AD), while the SAM/resistant 1 (SAMR1) mouse model shows normal features. Recent evidence has shown that long non-coding RNAs (lncRNAs) may play an important role in AD pathogenesis. However, a comprehensive and systematic understanding of the function of AD-related lncRNAs and their associated nearby coding genes in AD is still lacking. In this study, we collected the hippocampus, the main area of AD pathological processes, of SAMP8 and SAMR1 animals and performed microarray analysis to identify aberrantly expressed lncRNAs and their associated nearby coding genes, which may contribute to AD pathogenesis. We identified 3,112 differentially expressed lncRNAs and 3,191 differentially expressed mRNAs in SAMP8 mice compared to SAMR1 mice. More than 70% of the deregulated lncRNAs were intergenic and exon sense-overlapping lncRNAs. Gene Ontology (GO) and pathway analyses of the AD-related transcripts were also performed and are described in detail, which imply that metabolic process reprograming was likely related to AD. Furthermore, six lncRNAs and six mRNAs were selected for further validation of the microarray results using quantitative PCR, and the results were consistent with the findings from the microarray. Moreover, we analyzed 780 lincRNAs (also called long "intergenic" non-coding RNAs) and their associated nearby coding genes. Among these lincRNAs, AK158400 had the most genes nearby (n = 13), all of which belonged to the histone cluster 1 family, suggesting regulation of the nucleosome structure of the chromosomal fiber by affecting nearby genes during AD progression. In addition, we also identified 97 aberrant antisense lncRNAs and their associated coding genes. It is likely that these dysregulated lncRNAs and their associated nearby coding genes play a role in the development and/or progression of AD.Item Hypoxia-driven ncRNAs in breast cancer(Frontiers Media, 2023-07-31) Al-Zuaini, Hashim H.; Rafiq Zahid, Kashif; Xiao, Xiangyan; Raza, Umar; Huang, Qiyuan; Zeng, Tao; Radiation Oncology, School of MedicineLow oxygen tension, or hypoxia is the driving force behind tumor aggressiveness, leading to therapy resistance, metastasis, and stemness in solid cancers including breast cancer, which now stands as the leading cause of cancer-related mortality in women. With the great advancements in exploring the regulatory roles of the non-coding genome in recent years, the wide spectrum of hypoxia-responsive genome is not limited to just protein-coding genes but also includes multiple types of non-coding RNAs, such as micro RNAs, long non-coding RNAs, and circular RNAs. Over the years, these hypoxia-responsive non-coding molecules have been greatly implicated in breast cancer. Hypoxia drives the expression of these non-coding RNAs as upstream modulators and downstream effectors of hypoxia inducible factor signaling in the favor of breast cancer through a myriad of molecular mechanisms. These non-coding RNAs then contribute in orchestrating aggressive hypoxic tumor environment and regulate cancer associated cellular processes such as proliferation, evasion of apoptotic death, extracellular matrix remodeling, angiogenesis, migration, invasion, epithelial-to-mesenchymal transition, metastasis, therapy resistance, stemness, and evasion of the immune system in breast cancer. In addition, the interplay between hypoxia-driven non-coding RNAs as well as feedback and feedforward loops between these ncRNAs and HIFs further contribute to breast cancer progression. Although the current clinical implications of hypoxia-driven non-coding RNAs are limited to prognostics and diagnostics in breast cancer, extensive explorations have established some of these hypoxia-driven non-coding RNAs as promising targets to treat aggressive breast cancers, and future scientific endeavors hold great promise in targeting hypoxia-driven ncRNAs at clinics to treat breast cancer and limit global cancer burden.Item Long non-coding RNAs as critical regulators and novel targets in cervical cancer: current status and future perspectives(Springer Nature, 2023) Ranga, Shalu; Yadav, Ritu; Chhabra, Ravindresh; Chauhan, Meenakshi B.; Tanwar, Mukesh; Yadav, Chetna; Kadian, Lokesh; Ahuja, Parul; Medicine, School of MedicineCervical cancer is among the leading causes of cancer-associated mortality in women. In spite of vaccine availability, improved screening procedures, and chemoradiation therapy, cervical cancer remains the most commonly diagnosed cancer in 23 countries and the leading cause of cancer deaths in 36 countries. There is, therefore, a need to come up with novel diagnostic and therapeutic targets. Long non-coding RNAs (lncRNAs) play a remarkable role in genome regulation and contribute significantly to several developmental and disease pathways. The deregulation of lncRNAs is often observed in cancer patients, where they are shown to affect multiple cellular processes, including cell cycle, apoptosis, angiogenesis, and invasion. Many lncRNAs are found to be involved in the pathogenesis as well as progression of cervical cancer and have shown potency to track metastatic events. This review provides an overview of lncRNA mediated regulation of cervical carcinogenesis and highlights their potential as diagnostic and prognostic biomarkers as well as therapeutic targets for cervical cancer. In addition, it also discusses the challenges associated with the clinical implication of lncRNAs in cervical cancer.Item Tissue-specific Co-expression of Long Non-coding and Coding RNAs Associated with Breast Cancer(SpringerNature, 2016-09-06) Wu, Wenting; Wagner, Erin K.; Hao, Yangyang; Rao, Xi; Dai, Hongji; Han, Jiali; Chen, Jinhui; Storniolo, Anna Maria V.; Liu, Yunlong; He, Chunyan; Department of Epidemiology, Richard M. Fairbanks School of Public HealthInference of the biological roles of lncRNAs in breast cancer development remains a challenge. Here, we analyzed RNA-seq data in tumor and normal breast tissue samples from 18 breast cancer patients and 18 healthy controls and constructed a functional lncRNA-mRNA co-expression network. We revealed two distinctive co-expression patterns associated with breast cancer, reflecting different underlying regulatory mechanisms: (1) 516 pairs of lncRNA-mRNAs have differential co-expression pattern, in which the correlation between lncRNA and mRNA expression differs in tumor and normal breast tissue; (2) 291 pairs have dose-response co-expression pattern, in which the correlation is similar, but the expression level of lncRNA or mRNA differs in the two tissue types. We further validated our findings in TCGA dataset and annotated lncRNAs using TANRIC. One novel lncRNA, AC145110.1 on 8p12, was found differentially co-expressed with 127 mRNAs (including TOX4 and MAEL) in tumor and normal breast tissue and also highly correlated with breast cancer clinical outcomes. Functional enrichment and pathway analyses identified distinct biological functions for different patterns of co-expression regulations. Our data suggested that lncRNAs might be involved in breast tumorigenesis through the modulation of gene expression in multiple pathologic pathways.