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Identification and integrated analysis of differentially expressed long non-coding rnas associated with periodontitis in humans

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JOUrnaL OF PERIODONTAL RESEARCH 2021年第4期56卷 679-689页

作者： Lin, Yifan Jin, Lijian Tong, Wai Man Leung, Yiu Yan Gu, Min Yang, Yanqi Univ Hong Kong Fac Dent Orthodont Hong Kong Peoples R China Univ Hong Kong Fac Dent Periodontol & Implant Dent Hong Kong Peoples R China Univ Hong Kong Fac Dent Cent Res Lab Hong Kong Peoples R China Univ Hong Kong Fac Dent Oral & Maxillofacial Surg Hong Kong Peoples R China

Background and Objective Long non-coding rnas (lncrnas) can act as competing endogenous rnas (cernas) to compete for micro-rnas (mirnas) in regulation of downstream genes, various biological functions and diseases. Yet, the expression and regulation of lncrnas in periodontitis are not fully understood. The objective of the study was to identify potential genes (lncrna, messenger rna [mrna] and mirna) involved in periodontitis, construct lncrna-mirna-mrna cerna networks, explore gene functions and validate gene expressions. Material and Methods The data sets for the lncrna, mrna and mirna expression profiles in gingival samples from periodontally healthy subjects and chronic periodontitis patients were obtained from the Gene Expression Omnibus. The differentially expressed lncrnas (DElncrnas), mrnas (DEmrnas) and mirnas (DEmirnas) were identified, and cerna networks were then constructed. The expression of DElncrnas and DEmrnas was examined by quantitative real-time polymerase chain reaction (qPCR). Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed for exploring the potential functions and biological pathways. Results The GSE80715 and GSE54710 data sets were retrieved. Subsequently, 26 DElncrnas, 436 DEmrnas and 12 DEmirnas were identified (|fold change| >= 2, adjusted p < 0.05). Further bioinformatics analysis contributed to establishment of the cerna networks, which consisted of 10 DElncrnas, 11 DEmirnas and 83 DEmrnas. Notably, the qPCR results showed a marked decrease in the expression of lncrna H19 and two mrnas (NOS1 and MAPT) which further supported the identified cerna network. The GO results revealed that the up-regulated mrnas were significantly enriched in inflammatory processes, whilst the down-regulated mrnas were enriched in cellular potentials. Conclusion Non-coding rnas are critically involved in the regulatory mechanisms in the pathogenesis of periodontitis. Further study is warranted

关键词： gene expression and regulatory networks non‐ protein‐ coding rna pathogenesis periodontitis

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A ten N6-methyladenosine-related long non-coding rnas signature predicts prognosis of triple-negative breast cancer

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JOUrnaL OF CLINICAL LABORATORY ANALYSIS 2021年第6期35卷 e23779-e23779页

作者： Wu, Jie Cai, Yan Zhao, Gaiping Li, Maolan Shanghai Jiao Tong Univ Sch Naval Architecture Ocean & Civil Engn Key Lab Hydrodynam Minist Educ Shanghai Peoples R China Southeast Univ Sch Biol Sci & Med Engn Nanjing Peoples R China Univ Shanghai Sci & Technol Sch Med Instrument & Food Engn Shanghai Peoples R China Shanghai Res Ctr Biliary Tract Dis Shanghai Peoples R China

Background Patients with triple-negative breast cancer (TNBC) face a major challenge of the poor prognosis, and N6-methyladenosine-(m6A) mediated regulation in cancer has been proposed. Therefore, this study aimed to explore the prognostic roles of m6A-related long non-coding rnas (Lncrnas) in TNBC. Methods Clinical information and expression data of TNBC samples were collected from TCGA and GEO databases. Pearson correlation, univariate, and multivariate Cox regression analysis were employed to identify independent prognostic m6A-related Lncrnas to construct the prognostic score (PS) risk model. Receiver operating characteristic (ROC) curve was used to evaluate the performance of PS risk model. A competing endogenous rna (cerna) network was established for the functional analysis on targeted mrnas. Results We identified 10 independent prognostic m6A-related Lncrnas (SAMD12-AS1, BVES-AS1, LINC00593, MIR205HG, LINC00571, ANKRD10-IT1, CIRBP-AS1, SUCLG2-AS1, BLACAT1, and HOXB-AS1) and established a PS risk model accordingly. Relevant results suggested that TNBC patients with lower PS had better overall survival status, and ROC curves proved that the PS model had better prognostic abilities with the AUC of 0.997 and 0.864 in TCGA and GSE76250 datasets, respectively. Recurrence and PS model status were defined as independent prognostic factors of TNBC. These ten Lncrnas were all differentially expressed in high-risk TNBC compared with controls. The cerna network revealed the regulatory axes for nine key Lncrnas, and mrnas in the network were identified to function in pathways of cell communication, signaling transduction and cancer. Conclusion Our findings proposed a ten-m6A-related Lncrnas as potential biomarkers to predict the prognostic risk of TNBC.

关键词： cerna network long non‐ coding rna N6‐ methyladenosine prognostic signature triple‐ negative breast cancer

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Modifications of rna in cancer: a comprehensive review

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MOLECULAR BIOLOGY REPORTS 2025年第1期52卷 1-19页

作者： Ranga, Shalu Yadav, Ritu Chauhan, Meenakshi Chhabra, Ravindresh Ahuja, Parul Balhara, Nikita Maharshi Dayanand Univ Dept Genet Rohtak 124001 Haryana India Pandit Bhagwat Dayal Sharma Univ Hlth Sci Dept Obstet & Gynaecol Rohtak 124001 Haryana India Cent Univ Panjab Dept Biochem Bathinda 151401 Panjab India

rna modifications play essential roles in post-transcriptional gene regulation and have emerged as significant contributors to cancer biology. Major chemical modifications of rna include N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), pseudouridine (psi), and N7-methylguanosine (m7G). Their dynamic regulation highlights their roles in gene expression modulation, rna stability, and translation. Advanced high-throughput detection methods, ranging from liquid chromatography-mass spectrometry and high-performance liquid chromatography to next-generation sequencing (NGS) and nanopore direct rna sequencing, have enabled detailed studies of rna modifications in cancer cells. Aberrant rna modifications are associated with the dysregulation of tumor suppressor genes and oncogenes, influencing cancer progression, therapy resistance, and immune evasion. Emerging research suggests the therapeutic potential of targeting rna-modifying enzymes and their inhibitors in cancer treatment. This review compiles and analyzes the latest findings on rna modifications, presenting an in-depth discussion of the diverse chemical alterations that occur in rna and their profound implications in cancer biology. It integrates fundamental principles with cutting-edge research, offering a holistic perspective on how rna modifications influence gene expression, tumor progression, and therapeutic resistance. It emphasizes the need for further studies to elucidate the complex roles of rna modifications in cancer, as well as the potential for multimodality therapeutic strategies that exploit the dynamic and reversible nature of these epitranscriptomic marks. It also attempts to highlight the challenges, gaps, and limitations of rna modifications in cancer that should be tackled before their functional implications. Understanding the interplay between rna modifications, cancer pathways, and their inhibitors will be crucial for developing promising rna-based therapeutic approac

关键词： Chemical modifications rna methylation coding rna Non-coding rna Tumorigenesis Epitranscriptomic marks rna-modifying enzymes Therapeutic strategies

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Identification of autophagy-related gene and lncrna signatures in the prognosis of HNSCC

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ORAL DISEASES 2023年第1期29卷 138-153页

作者： Li, Qilin Wang, Jing Meng, Xinyao Chen, Weimin Feng, Jiexiong Mao, Jing Huazhong Univ Sci & Technol Tongji Hosp Dept Stomatol Tongji Med Coll Wuhan Peoples R China Huazhong Univ Sci & Technol Tongji Hosp Dept Pediat Surg Tongji Med Coll Wuhan 430030 Peoples R China

Objective The aim of this study was to identify prognostic autophagy-related genes and lncrnas to predict clinical outcomes in head and neck squamous cell carcinoma (HNSCC). Subjects and methods Differentially expressed autophagy-related genes and autophagy-related lncrnas were identified by comparing pare-carcinoma and carcinoma samples of HNSCC. And then, we constructed an ARG and an AR-lncrna signature risk score. Receiver operating characteristic (ROC) curve analyses were performed to assess the prognostic prediction capacity. Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO) functional annotation were used to analysis the functions of ARGs and AR-lncrnas. Results Six ARGs and thirteen AR-lncrnas were identified in the ARG and AR-lncrna signatures, and overall survival (OS) in the high-risk group was significantly shorter than the low-risk group. ROC analysis showed the ARG and AR-lncrna signatures have excellent ability of predicting the total OS of patients with HNSCC. What's more, GSEA and GO functional annotation proved that autophagy-related pathways are mainly enriched in the high-risk group. Conclusions These findings indicated that our ARG signature and AR-lncrna signature could be considered to predict the prognosis of patients with HNSCC and provide a deep understanding of the biological mechanisms of autophagy in HNSCC.

关键词： autophagy HNSCC long non‐ coding rna prognosis

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Genome-wide characterization of coding and non-coding rnas in the ovary of honeybee workers and queens

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APIDOLOGIE 2020年第5期51卷 777-792页

作者： Chen, Xiao Shi, Wei Chinese Acad Agr Sci Inst Apicultural Res Beijing Peoples R China Xiangshan Beigou 1 Beijing 100093 Peoples R China

Adult honeybee queens and workers drastically differ in ovary state and ovary size. However, this reproductive bias is only partially understood from the view of a single rna type. In this study, we predicted 10,271 mrnas, 7235 lncrnas, 11,794 circrnas, and 164 mirnas in the ovary of honeybee workers through bioinformatics. Combining rna sequencing data of honeybee virgin queens, 4385 mrnas, 2390 lncrnas, 5602 circrnas, and 75 mirnas were differentially expressed in workers compared with virgins. Compared with egg-laying queens, 6536 mrnas, 3130 lncrnas, 5751 circrnas, and 81 mirnas were differentially expressed in workers. Further, functional annotation revealed that neural regulation was closely related to ovary state. Moreover, the potential interactions among circrnas, mirnas, lncrnas, and mrnas revealed that vitellogenin, ecdysone-induced protein 74, ame_circ_0001176, and ame_circ_0001243 might play critical roles in the competing endogenous rna network. These findings suggest that the integrative rna networks have potential effects in ovarian phenotype differences in honeybees.

关键词： Apis mellifera ligustica ovary caste difference coding rna non-coding rna

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Extracellular vesicle-mediated regulation of tumor angiogenesis- implications for anti-angiogenesis therapy

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JOUrnaL OF CELLULAR AND MOLECULAR MEDICINE 2021年第6期25卷 2776-2785页

作者： Zhang, Shuqiong Yang, Junyao Shen, Lisong Shanghai Jiao Tong Univ Xinhua Hosp Dept Clin Lab Sch Med Shanghai 200092 Peoples R China

Angiogenesis plays an important role in tumour progression. However, anti-angiogenesis therapy of inhibiting pro-angiogenic factors failed to meet expectations in certain types of tumour in clinical trials. Recent studies reveal that tumour-derived extracellular vesicles (EVs) are essential in tumour angiogenesis and anti-angiogenesis drug resistance. This function has most commonly been attributed to EV contents including proteins and non-coding rnas. Here, we summarize the recent findings of tumour-derived EV contents associated with regulating angiogenesis and illustrate the underlying mechanisms. In addition, the roles of EVs in tumour microenvironmental cells are also illustrated with a focus on how EVs participate in cell-cell communication, contributing to tumour-mediated angiogenesis. It will help offer new perspectives on developing targets of anti-angiogenesis drugs and improve the efficacy of anti-angiogenesis therapies based on tumour-derived EVs.

关键词： angiogenesis drug resistance endothelial cells extracellular vesicles non‐ coding rna

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Inhibition of miR-188-5p alleviates hepatic fibrosis by significantly reducing the activation and proliferation of HSCs through PTEN/PI3K/AKT pathway

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JOUrnaL OF CELLULAR AND MOLECULAR MEDICINE 2021年第8期25卷 4073-4087页

作者： Riaz, Farooq Chen, Qian Lu, Kaikai Osoro, Ezra Kombo Wu, Litao Feng, Lina Zhao, Rong Yang, Luyun Zhou, Yimeng He, Yingli Zhu, Li Du, Xiaojuan Sadiq, Muhammad Yang, Xudong Li, Dongmin Xi An Jiao Tong Univ Sch Basic Med Sci Dept Biochem & Mol Biol Hlth Sci Ctr Xian 710061 Shaanxi Peoples R China Minist Educ Key Lab Environm & Genes Related Dis Xian Shaanxi Peoples R China Xi An Jiao Tong Univ Dept Infect Dis Affiliated Hosp 1 Xian Peoples R China

Persistent hepatic damage and chronic inflammation in liver activate the quiescent hepatic stellate cells (HSCs) and cause hepatic fibrosis (HF). Several micrornas regulate the activation and proliferation of HSCs, thereby playing a critical role in HF progression. Previous studies have reported that miR-188-5p is dysregulated during the process of HF. However, the role of miR-188-5p in HF remains unclear. This study investigated the potential role of miR-188-5p in HSCs and HF. Firstly, we validated the miR-188-5p expression in primary cells isolated from liver of carbon tetrachloride (CCl4)-induced mice, TGF-beta 1-induced LX-2 cells, livers from 6-month high-fat diet (HFD)-induced rat and 4-month HFD-induced mice NASH models, and human non-alcoholic fatty liver disease (NAFLD) patients. Furthermore, we used miR-188-5p inhibitors to investigate the therapeutic effects of miR-188-5p inhibition in the HFD + CCl4 induced in vivo model and the potential role of miR-188-5p in the activation and proliferation of HSCs. This present study reported that miR-188-5p expression is significantly increased in the human NAFLD, HSCs isolated from liver of CCl4 induced mice, and in vitro and in vivo models of HF. Mimicking the miR-188-5p resulted in the up-regulation of HSC activation and proliferation by directly targeting the phosphatase and tensin homolog (PTEN). Moreover, inhibition of miR-188-5p reduced the activation and proliferation markers of HSCs through PTEN/AKT pathway. Additionally, in vivo inhibition of miR-188-5p suppressed the HF parameters, pro-fibrotic and pro-inflammatory genes, and fibrosis. Collectively, our results uncover the pro-fibrotic role of miR-188-5p. Furthermore, we demonstrated that miR-188-5p inhibition decreases the severity of HF by reducing the activation and proliferation of HSCs through PTEN/AKT pathway.

关键词： hepatic fibrosis hepatic stellate cell MiR‐ 188‐ 5p non‐ alcoholic fatty liver disease non‐ coding rna PTEN AKT pathway

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Dysregulated epigenetic modifications in psoriasis

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EXPERIMENTAL DERMATOLOGY 2021年第8期30卷 1156-1166页

作者： Zeng, Chang Tsoi, Lam C. Gudjonsson, Johann E. Univ Michigan Dept Dermatol Ann Arbor MI 48109 USA Univ Michigan Dept Computat Med & Bioinformat Med Sch Ann Arbor MI 48109 USA Univ Michigan Dept Biostat Med Sch Ann Arbor MI 48109 USA A Alfred Taubman Med Res Inst Ann Arbor MI USA

The observed incidence of psoriasis has been gradually increasing over time (J Am Acad Dermatol, 03, 2009, 394), but the underlying pathogenic factors have remained unclear. Recent studies suggest the importance of epigenetic modification in the pathogenesis of psoriasis. Aberrant epigenetic patterns including changes in DNA methylation, histone modifications and non-coding rna expression are observed in psoriatic skin. Reversing these epigenetic mechanisms has showed improvement in psoriatic phenotypes, making epigenetic therapy a potential avenue for psoriasis treatment. Here, we summarize relevant evidence for epigenetic dysregulation contributing to psoriasis susceptibility and pathogenesis, and the factors responsible for epigenetic modifications, providing directions for potential future clinical avenues.

关键词： DNA methylation epigenetics histone modification non‐ coding rna psoriasis

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High expression of novel biomarker KRT16P3 promotes the progression of tongue squamous cell carcinoma and predicts poor prognosis

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JOUrnaL OF ORAL PATHOLOGY & MEDICINE 2021年第4期50卷 385-393页

作者： Yang, Yifan Feng, Ling Ma, Hongzhi Wang, Ru Fang, Jugao Capital Med Univ Beijing Tongren Hosp Dept Otolaryngol Head & Neck Surg Beijing Peoples R China

Background Overexpression of long non-coding rnas (lncrnas) reveals the abnormal pathological processes in many human cancers. KRT16P3, a novel overexpressed lncrna in tongue squamous cell carcinoma (TSCC), was identified by previous lncrna microarrays. However, the role of KRT16P3 in TSCC is not clear. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of KRT16P3 in TSCC tissues and cells. Next, the relationships between KRT16P3 and the clinical significance of TSCC patients were analyzed. Additionally, Cell Counting Kit-8, 5-Bromo-2-deoxyuridine (BrdU) incorporation assay, cell colony formation assay, flow cytometry cell apoptosis analysis, scratch wound healing assay, transwell invasion assay were used to explore the biological function of KRT16P3. Western blot and qRT-PCR were used to determine the expression of epithelial-mesenchymal transition (EMT) markers. The pathway changes after KRT16P3 knockdown were detected by Western blot. Results We found KRT16P3 expression is significantly upregulated in TSCC tissues and positively associated with advanced clinicopathological features of TSCC patients, and it may serve as a poor prognostic factor. Functionally, KRT16P3 knockdown inhibits proliferation, migration, invasion and promotes apoptosis of TSCC cells. Furthermore, we also revealed that KRT16P3 knockdown suppresses EMT and JAK2/STAT3 signaling pathway. Conclusion Our results validated that KRT16P3 can modulate the malignant progression, EMT process, and JAK2/STAT3 signaling pathway of TSCC, which might also serve as a novel prognostic biomarker and an attractive target for TSCC patients.

关键词： long non‐ coding rna prognosis progression tongue squamous cell carcinoma

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Identification of novel dysregulated circular rnas in early-stage breast cancer

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JOUrnaL OF CELLULAR AND MOLECULAR MEDICINE 2021年第8期25卷 3912-3921页

作者： Rao, Arunagiri Kuha Deva Magendhra Arvinden, Vittal Rangan Ramasamy, Deepa Patel, Krishna Meenakumari, Balaiah Ramanathan, Priya Sundersingh, Shirley Sridevi, Velusami Rajkumar, Thangarajan Herceg, Zdenko Gowda, Harsha Mani, Samson Canc Inst WIA Dept Mol Oncol 38 Sardar Patel Rd Chennai 600036 Tamil Nadu India ITPL Inst Bioinformat Bangalore Karnataka India Amrita Vishwa Vidyapeetham Amrita Sch Biotechnol Kollam India Canc Inst WIA Dept Oncopathol Chennai Tamil Nadu India Canc Inst WIA Dept Surg Oncol Chennai Tamil Nadu India Int Agcy Res Canc IARC Epigenet Grp Lyon France Manipal Acad Higher Educ MAHE Manipal Karnataka India Royal Brisbane Hosp QLD QIMR Berghofer Brisbane Qld Australia

Breast cancer is a major cause of cancer-related death in women worldwide. Non-coding rnas are a potential resource to be used as an early diagnostic biomarker for breast cancer. Circular rnas are a recently identified group of non-coding rna with a significant role in disease development with potential utility in diagnosis/prognosis in cancer. In this study, we identified 26 differentially expressed circular rnas associated with early-stage breast cancer. rna sequencing and two circrna detection tools (find_circ and DCC) were used to understand the circrna expression signature in breast cancer. We identified hsa_circ_0006743 (circJMJD1C) and hsa_circ_0002496 (circAPPBP1) to be significantly up-regulated in early-stage breast cancer tissues. Co-expression analysis identified four pairs of circrna-mirna (hsa_circ_0023990 : hsa-miR-548b-3p, hsa_circ_0016601 : hsa_miR-1246, hsa_circ_0001946 : hsa-miR-1299 and hsa_circ_0000117:hsa-miR-502-5p) having potential interaction. The mirna target prediction and network analysis revealed mrna possibly regulated by circrnas. We have thus identified circrnas of diagnostic implications in breast cancer and also observed circrna-mirna interaction which could be involved in breast cancer development.

关键词： breast cancer circrna as microrna precursor circrna‐ microrna interaction circular rna non‐ coding rna

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