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long non-coding rna HOTAIR in circulatory exosomes is correlated with ErbB2/HER2 positivity in breast cancer

BREAST 2019年第0期46卷 64-69页

作者： Wang, Yuan-Liang Liu, Liang-Chih Hung, Yu Chen, Chih-Jung Lin, You-Zhe Wu, Wan-Rong Wang, Shao-Chun China Med Univ Hosp Ctr Mol Med Taichung 40447 Taiwan China Med Univ Dept Med Coll Med Taichung 40402 Taiwan China Med Univ Grad Inst Biomed Sci Coll Med Taichung 40402 Taiwan China Med Univ Hosp Dept Surg Taichung 40447 Taiwan Univ Cincinnati Dept Canc Biol Cincinnati OH 45267 USA Asia Univ Dept Biotechnol Taichung 413 Taiwan China Med Univ Acad Sinica PhD Program Canc Biol & Drug Dev Taichung Taiwan China Med Univ Acad Sinica PhD Program Translat Med Taichung Taiwan

Cancer cells are known to produce and secret extracellular vesicles for intercellular communication through the carried cargos. HOTAIR (HOX transcript antisense intergenic rna), a well-studied long non-coding rna (Incrna), plays a critical role in cancer progression. In several cancer types it has been shown that HOTAIR-containing exosomes are produced by cancer cells. Here we show that circulatory exosomal HOTAIR is present in breast cancer patients and explores the pathological correlation with the disease. Exosomes were isolated by matrix-based precipitation from conditioned media of cultured breast cancer cell lines as well as blood samples of recently recruited breast cancer patients. HOTAIR rna in exosomes was detected by quantitative reverse transcriptase-mediated polymerase chain reaction (qRT-PCR). Expression of exosomal HOTAIR was positively correlated with status of the receptor tyrosine kinase (RTK) ErbB2 (also known as HER2/neu) in tumor tissues. The causal correlation of ErbB2 and HOTAIR was validated in isogenic breast cancer cell lines with and without ectopic ErbB2 expression. Our finding provides a molecular basis to develop novel liquid biopsy biomarkers and targeted therapies with improved precision for malignant breast cancer. (C) 2019 Elsevier Ltd. All rights reserved.

关键词： Extracellular vesicle Exosome long non-coding rna HOTAIR Breast cancer HER2/ErbB2

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long non-coding rna FAM83H-AS1 as an emerging marker for diagnosis, prognosis and therapeutic targeting of cancer

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CELL BIOCHEMISTRY AND FUNCTION 2021年第3期39卷 350-356页

作者： El-Ashmawy, Nahla E. Al-Ashmawy, Ghada M. Hamouda, Sara M. Tanta Univ Fac Pharm Dept Biochem Al Geish St Tanta 31527 El Gharbia Egypt

Incidence and mortality rates of cancer continue to increase greatly despite the improved diagnostic and therapeutic methods. Based on GLOBOCAN estimates, the numbers of new cancer cases reported in 2018 were similar to 18.1 million, while the numbers of cancer mortalities were similar to 9.6 million. It remains difficult to diagnose most cancer patients at early stages. Although cancer therapy market is rapidly evolving, the effectiveness of therapy is still inadequate. Therefore, exploring new biomarkers for diagnosis, prognosis and treatment is essential for cancer management. long non-coding rnas (lncrnas) are unique regulatory molecules that control several cellular processes and are implicated in diverse human diseases including cancer. Lncrnas could serve as potential biomarkers for cancer patients to aid diagnosis and determine prognosis. In addition, numerous lncrnas have proved their ability to predict response to cancer treatment. FAM83H antisense rna 1 (FAM83H-AS1) is among those highly dysregulated lncrnas in cancer. FAM83H-AS1 was demonstrated to participate in the progression of different malignancies and also shown to play a vital role in diagnosis, prognosis and treatment. Here, we analyse recent studies concerning the oncogenic role and molecular mechanisms of lncrna FAM83H-AS1 in the following cancer types: bladder, breast, lung, hepatocellular, colorectal, gastric, pancreatic, ovarian, cervical cancer as well as glioma.

关键词： cancer diagnosis FAM83H-AS1 long non-coding rna molecular mechanisms prognosis

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long non-coding rna: Functional agent for disease traits

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rna BIOLOGY 2017年第5期14卷 522-535页

作者： Jain, Sriyans Thakkar, Nirav Chhatai, Jagamohan Bhadra, Manika Pal Bhadra, Utpal CSIR Ctr Cellular & Mol Biol Funct Genom & Gene Silencing Grp Hyderabad Andhra Pradesh India Indian Inst Chem Technol Ctr Chem Biol Hyderabad Andhra Pradesh India

In recent years, long non-coding rnas (lncrnas) have attracted the attention of researchers with their involvement in all facets of life. Lncrnas are transcripts of more than 200 nucleotides which lack defined protein coding potential. Although they do not code for proteins, a large number of them are involved in regulating gene expression and translation. The presence of numerous lncrnas in the human genome has prompted us to investigate the contribution of these molecules to human biology and medicine. In this review, we present the potential role of lncrnas interlinked to different human diseases and genetic disorders. We also describe their role in cellular differentiation and aging and discuss their potential importance as biomarkers and as therapeutic agents.

关键词： Biomarkers epigenetics gene regulation human diseases long non-coding rna therapeutic agents

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long non-coding rna TUG1 is up-regulated in hepatocellular carcinoma and promotes cell growth and apoptosis by epigenetically silencing of KLF2

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MOLECULAR CANCER 2015年第1期14卷 1-12页

作者： Huang, Ming-De Chen, Wen-Ming Qi, Fu-Zhen Sun, Ming Xu, Tong-Peng Ma, Pei Shu, Yong-qian Nanjing Med Univ Huaian Peoples Hosp 1 Dept Med Oncol Huaian City 223301 Jiangsu Peoples R China Jining 1 Peoples Hosp Dept Oncol Jining City 272011 Shandong Peoples R China Nanjing Med Univ Huaian Peoples Hosp 1 Dept Hepatopancreatobiliary Surg Huaian City 223300 Jiangsu Peoples R China Nanjing Med Univ Dept Biochem & Mol Biol Nanjing Jiangsu Peoples R China Nanjing Med Univ Affiliated Hosp 1 Dept Oncol Nanjing Jiangsu Peoples R China

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide, and the biology of this cancer remains poorly understood. Recent evidence indicates that long non-coding rnas (lncrnas) are found to be dysregulated in a variety of cancers, including HCC. Taurine Up-regulated Gene 1 (TUG1), a 7.1-kb lncrna, recruiting and binding to polycomb repressive complex 2 (PRC2), is found to be disregulated in non-small cell lung carcinoma (NSCLC) and esophageal squamous cell carcinoma (ESCC). However, its clinical significance and potential role in HCC remain unclear. Methods and results: In this study, expression of TUG1 was analyzed in 77 HCC tissues and matched normal tissues by using quantitative polymerase chain reaction (qPCR). TUG1 expression was up-regulated in HCC tissues and the higher expression of TUG1 was significantly correlated with tumor size and Barcelona Clinic Liver Cancer (BCLC) stage. Moreover, silencing of TUG1 expression inhibited HCC cell proliferation, colony formation, tumorigenicity and induced apoptosis in HCC cell lines. We also found that TUG1 overexpression was induced by nuclear transcription factor SP1 and TUG1 could epigeneticly repress Kruppel-like factor 2 (KLF2) transcription in HCC cells by binding with PRC2 and recruiting it to KLF2 promoter region. Conclusion: Our results suggest that lncrna TUG1, as a growth regulator, may serve as a new diagnostic biomarker and therapy target for HCC.

关键词： long non-coding rna TUG1 HCC Proliferation KLF2

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long non-coding rna GAS5 polymorphism predicts a poor prognosis of acute myeloid leukemia in Chinese patients via affecting hematopoietic reconstitution

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LEUKEMIA & LYMPHOMA 2017年第8期58卷 1948-1957页

作者： Yan, Han Zhang, Dao-Yu Li, Xi Yuan, Xiao-Qing Yang, Yong-long Zhu, Ke-Wei Zeng, Hui Li, Xiao-Lin Cao, Shan Zhou, Hong-Hao Zhang, Wei Chen, Xiao-Ping Cent S Univ Xiangya Hosp Dept Clin Pharmacol 110 Xiang Ya Changsha 410008 Hunan Peoples R China Cent S Univ Inst Clin Pharmacol Hunan Key Lab Pharmacogenet Changsha Hunan Peoples R China Hunan Prov Cooperat Innovat Ctr Mol Target New Dr Hengyang Peoples R China Cent S Univ Haikou Peoples Hosp Affiliated Haikou Hosp Xiangya Med Sch Haikou Peoples R China Cent S Univ Xiangya Hosp Dept Hematol Changsha Hunan Peoples R China

Whether long non-coding rna (lncrna) single-nucleotide polymorphisms (SNPs) affect prognosis of acute myeloid leukemia (AML) remains unknown. To search the association between lncrna SNPs and AML outcomes, thirty tagSNPs in five lncrnas were genotyped in 313 AML patients. Survival analysis indicated that GAS5 rs55829688 (T>C) was significantly associated with prognosis of AML (p=0.018). Patients with rs55829688CC genotype showed higher GAS5 expression in peripheral blood mononuclear cells (PBMCs) (p=0.025) and harbored a longer platelets recovery (p=0.040) than carriers of rs55829688T allele. In vitro study indicated that GAS5 promoter harboring the rs55829688C allele showed marginally increased reporter gene activity (p=0.019), and the promoter activity was increased by TP63 in a dose-dependent manner (P=0.001). Moreover, GAS5 higher expression predict shorter AML overall survival (OS), which validated in GEO GSE12417 dataset (p=0.011). In conclusion, rs55829688 polymorphism could increase GAS5 expression by interacting with TP63, which might aggravate the myelosuppression and in turn lead to poor prognosis in AML. Trail registration number: ChiCTR-PPC-14005297.

关键词： Growth arrest specific 5 single nucleotide polymorphism acute myeloid leukemia long non-coding rna promoter

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long non-coding rna SAP30L-AS1 promotes prostate cancer growth through repressing SAP30L

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GENE 2019年 690卷 120-128页

作者： Qin, Xiangcheng Zhu, Weizhi Lu, Aimei Wang, Gang Ye, Xiaolei Weng, Guobin Ningbo Urol & Nephrol Hosp Dept Urol Ningbo 315192 Zhejiang Peoples R China Ningbo Urol & Nephrol Hosp Dept Ultrasonog Ningbo 315192 Zhejiang Peoples R China Ningbo Inst Med Sci Ningbo 315020 Zhejiang Peoples R China

Accumulating evidences have demonstrated the importance of long non-coding rnas (lncrnas) in initiation and progression of various cancers, including prostate cancer. Lncrna SAP30L-AS1 is previously identified in the plasma of prostate cancer patients. In this study, we further investigated the expression of SAP30L-AS1 in prostate cancer tissues and cell lines. Moreover, we explored the biological roles and mechanisms of action of SAP30L-AS1 in prostate cancer. The expression of SAP30L-AS1 is found to be increased in prostate cancer tissues and cell lines compared with adjacent noncancerous tissues and normal prostate epithelial cell line, respectively. Increased expression of SAP30L-AS1 is associated with greater Gleason score, advanced pathological T stage, and poor over survival of prostate cancer patients. Functional assays demonstrated that ectopic expression of SAP30L-AS1 promotes prostate cancer proliferation and inhibits prostate cancer apoptosis. SAP30L-AS1 knockdown represses prostate cancer proliferation and induces prostate cancer apoptosis. Furthermore, SAP30L-AS1 knockdown represses prostate cancer xenograft growth in vivo. Mechanistic investigation revealed that SAP30L-AS1 physically binds to the promoter of SAP30L and represses SAP30L expression. The expression of SAP30L is negatively associated with that of SAP30L-AS1 in prostate cancer tissues. Rescue assays demonstrated that overexpression of SAP30L attenuated the roles of SAP30L-AS1 in promoting prostate cancer proliferation and inhibiting prostate cancer apoptosis. In conclusion, SAP30L-AS1 is upregulated and has oncogenic roles in prostate cancer via repressing SAP30L. Our data suggest that SAP30L-AS1 may be a promising prognostic biomarker and therapeutic target for prostate cancer.

关键词： long non-coding rna Prostate cancer Proliferation Apoptosis SAP30L

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long non-coding rna BZRAP1-AS1 silencing suppresses tumor angiogenesis in hepatocellular carcinoma by mediating THBS1 methylation

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JOUrnaL OF TRANSLATIONAL MEDICINE 2019年第1期17卷 1-15页

作者： Wang, Weiwei Chen, Guoyong Wang, Bing Yuan, Zhenhua Liu, Guangbo Niu, Biao Chen, Yongfeng Zhou, Shaotang He, Junchuang Xue, Huanzhou Zhengzhou Univ Dept Hepatobiliary Surg Peoples Hosp Henan Prov Peoples Hosp 7 Weiwu Rd Zhengzhou 450003 Peoples R China

Background Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer associated with a high mortality. long non-coding rnas (lncrnas) have recently emerged as regulators in the development and progression of several cancers, and therefore represent an opportunity to uncover new targets for therapy. In the present study, we aimed to investigate the potential effect of lncrna BZRAP1-AS1 on the angiogenesis of HCC. Methods Microarray-based data analysis was initially employed to screen genes and lncrnas that are differentially expressed in HCC and the candidate BZRAP1-AS1 was identified as a hit. The expression of BZRAP1-AS1 and thrombospondin-1 (THBS1) in HCC tissues and cells were then determined using RT-qPCR. The gene methylation level was measured by methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP) assays. Next, the interactions between BZRAP1-AS1, DNA methyltransferase 3B (DNMT3b), and THBS1 were assessed by RIP, rna pull-down and ChIP assays. Finally, the roles of BZRAP1-AS1, DNMT3b and THBS1 in angiogenesis in vitro as well as tumorigenesis in vivo were evaluated by a battery of the gain- and loss-of function experiments. Results BZRAP1-AS1 was identified as a highly expressed lncrna in HCC tissues and cells. Down-regulation of BZRAP1-AS1 in HCC cells inhibited HUVEC proliferation, migration and angiogenesis. By interacting with DNMT3b, BZRAP1-AS1 induced methylation of the THBS1 promoter and inhibited the transcription of THBS1, resulting in promoted angiogenesis of HUVECs. Moreover, silencing of BZRAP1-AS1 repressed the angiogenesis as well as the tumor growth of HCC in vivo via up-regulating THBS1. Conclusion This study provides evidence that angiogenesis in HCC is hindered by silencing of BZRAP1-AS1. Thus, BZRAP1-AS1 may be a promising marker for the treatment of HCC.

关键词： Hepatocellular carcinoma long non-coding rna BZRAP1-AS1 DNA methyltransferase 3B Thrombospondin-1 DNA methylation Angiogenesis

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long non-coding rna lnc-CHAF1B-3 promotes renal interstitial fibrosis by regulating EMT-related genes in renal proximal tubular cells

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MOLECULAR THERAPY NUCLEIC ACIDS 2023年 31卷 139-150页

作者： Imai, Kentaro Ishimoto, Takuji Doke, Tomohito Tsuboi, Toshiki Watanabe, Yu Katsushima, Keisuke Suzuki, Miho Oishi, Hideto Furuhashi, Kazuhiro Ito, Yasuhiko Kondo, Yutaka Maruyama, Shoichi Nagoya Univ Grad Sch Med Dept Nephrol Nagoya 4668550 Japan Aichi Med Univ Dept Nephrol & Rheumatol Nagakute Aichi 4801195 Japan Nagoya Univ Grad Sch Med Dept Pathol Nagoya Aichi 4668550 Japan Komaki City Hosp Dept Hematol Komaki Aichi 4858520 Japan

Renal interstitial fibrosis (RIF) is a common pathological manifestation of chronic kidney diseases. Epithelial-mesenchymal transition (EMT) of tubular epithelial cells is considered a major cause of RIF. Although long non-coding rnas (lncrnas) are reportedly involved in various pathophysiological processes, the roles and underlying molecular mechanisms of lncrnas in the progression of RIF are poorly understood. In this study, we investigated the function of lncrnas in RIF. Microarray assays showed that expression of the lncrna lnc-CHAF1B-3 (also called claudin 14 antisense rna 1) was significantly upregulated in human renal proximal tubular cells by both transforming growth factor-b1 (TGF-b1) and hypoxic stimulation, accompanied with increased expression of EMT-related genes. Knock-down of lnc-CHAF1B-3 significantly suppressed TGF-b1-induced upregulated expression of collagen type I alpha 1, cadherin-2, plasminogen activator inhibitor-1, snail family transcriptional repressor I (SNAI1) and SNAI2. Quantitative reverse transcriptase PCR analyses of paraffin-embedded kidney biopsy samples from IgA nephropathy patients revealed lnc-CHAF1B-3 expression was correlated positively with urinary protein levels and correlated negatively with estimated glomerular filtration rate. In situ hybridization demonstrated that lnc-CHAF1B-3 is expressed only in proximal tubules. These findings suggest lnc-CHAF1B-3 affects the progression of RIF by regulating EMT-related signaling. Thus, lnc-CHAF1B-3 is a potential target in the treatment of RIF.

关键词： MT: non-coding rnas long non-coding rna lnc-CHAF1B-3 renal interstitial fibrosis epithelial-to-mesenchymal transition IgA nephropathy proximal tubular cell

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long non-coding rna XIST expression as a prognostic factor in human cancers: A meta-analysis

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INTErnaTIONAL JOUrnaL OF BIOLOGICAL MARKERS 2019年第4期34卷 327-333页

作者： Yin, Shuai Dou, Jiayu Yang, Guifang Chen, Fangfang Yangtze Univ Jingzhou Cent Hosp Clin Med Coll 2 Dept Gastroenterol Jingzhou Hubei Peoples R China Wuhan Univ Dept Pathol Zhongnan Hosp Wuhan Hubei Peoples R China McGill Univ Dept Microbiol & Immunol Montreal PQ Canada Wuhan Univ Dept Pathol Renmin Hosp Wuhan 430071 Hubei Peoples R China

A large number of literature has shown that high expression of X inactive-specific transcript (XIST) is associated with poor prognosis and metastasis of cancer in patients. However, most of this literature is limited by the small sample sizes and discrete outcomes. Therefore, a meta-analysis was performed to investigate the relation between XIST expression and tumor node metastasis (TNM) stage, lymph node metastasis, distant metastasis, and overall survival of cancer patients. We searched for literature in PubMed, Embase, and Web of Science. The pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the association of XIST expression with prognosis and clinicopathological characteristics of cancer patients. Finally, a total of 14 articles involving 1123 patients were included in this meta-analysis. The results suggested that high expression of XIST has a significant relationship with a relatively poor overall survival for patients with malignant tumors (HR 1.82;95% CI 1.32, 2.52;P = 0.0003). Moreover, high expression of XIST was significantly associated with poor TNM stage (OR 3.64;95% CI 2.62, 5.07;P < 0.0001), lymph node metastasis (OR 2.39;95% CI 1.65, 3.46;P < 0.0001) and distant metastasis (OR 2.84;95% CI 1.90, 4.23;P < 0.0001). In conclusion, high expression of lncrna XIST may be a predictive factor of poor prognosis in human cancers.

关键词： long non-coding rna XIST cancer meta-analysis

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long non-coding rna ZFAS1 is an unfavourable prognostic factor and promotes glioma cell progression by activation of the Notch signaling pathway

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BIOMEDICINE & PHARMACOTHERAPY 2017年 87卷 555-560页

作者： Gao, Kai Ji, Zhiwu She, Kun Yang, Qingyan Shao, Lianbin Hebei Univ Engn Affiliated Hosp Dept Neurosurg 81 Congtai Rd Handan 056002 Hebei Province Peoples R China

Survival of patients with glioma remains poor, which is largely attributed to active carcinogenesis. Accumulating evidence indicates that long non-coding rnas (lncrnas) play key roles in tumor initiation and progression. However, the function of lncrna ZFAS1 in glioma is still unclear. In the current study, we found that ZFAS1 was upregulated in glioma tissues and cell lines. High ZFAS1 expression in glioma tissues was significantly correlated with advanced tumor stage and poor overall survival. Furthermore, in vitro assays demonstrated that ZFAS1 inhibition significantly suppressed glioma cell proliferation, migration and invasion. Importantly, we further confirmed that epithelial-mesenchymal transition (EMT) and the Notch signaling pathway was inactivated in the glioma cells after ZFAS1 knockdown. Thus, our findings indicated that ZFAS1 could exhibit a tumor oncogenic role in glioma progression by regulating EMT and Notch signaling pathway. Lncrna ZFAS1 might serve as a therapeutic target for the treatment of glioma patients. (C) 2017 Elsevier Masson SAS. All rights reserved.

关键词： long non-coding rna ZFAS1 Glioma Epithelial-mesenchymal transition Notch signaling pathway

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