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long non-coding rna RP11-342L8.2, derived from rna sequencing and validated via RT-qPCR, is upregulated and correlates with disease severity in psoriasis patients

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IRISH JOUrnaL OF MEDICAL SCIENCE 2022年第6期191卷 2643-2649页

作者： Zhi, Yuanting Du, Jiru Qian, Miao Song, Ningjing Shanghai Jiao Tong Univ Tongren Hosp Dept Dermatol Sch Med Shanghai Peoples R China

Objective This study aimed to explore the dysregulated long non-coding rna (lncrna) expression profile in psoriatic tissue vs. normal skin tissue via rna sequencing (rna-seq), then further sort candidate lncrnas to be validated by reverse transcription quantitative polymerase chain reaction (RT-qPCR), in order to investigate the comprehensive linkage of lncrna with psoriasis. Methods Twenty-five psoriasis patients were consecutively enrolled, with their psoriatic and surrounding normal skin tissues obtained. Ten pairs of psoriatic and normal tissues were proposed to rna-seq. Then, top 6 differentially expressed lncrnas (DElncrna) were sorted as candidate lncrnas for validation by RT-qPCR in 25 pairs of samples. Results Principal component analysis (PCA) exhibited that lncrna profile clearly distinguished psoriatic tissue from normal tissue, so did heatmap. Volcano plot disclosed 412 upregulated and 625 downregulated DElncrnas in psoriatic tissue vs. normal tissue. Gene Ontology (GO) and Kyoko Encyclopedia of Genes and Genomes (KEGG) enrichment analyses exhibited that these DElncrnas were mainly enriched in immune, inflammation, or proliferation-related biological processes and pathways such as neutrophil degranulation, regulation of immune response, positive regulation of cell proliferation, and MAPK signaling pathway. By RT-qPCR validation, lncrnas RP11-22A3.2, RP11-342L8.2, and CTD-2006H14.2 were increased (all P < 0.001), while lncrnas AP000442.4, CCDC144NL-AS1, and MIR663AHG were decreased (all P < 0.01) in psoriatic tissue vs. normal tissue. Interestingly, psoriatic lncrna RP11-342L8.2 was also observed to positively correlated with psoriasis area and severity index (PASI) (r = 0.405, P = 0.045). Conclusion Our present study exhibits some evidence for the landscape of lncrnas implicated in psoriasis.

关键词： long non-coding rna Normal tissue Psoriasis Psoriatic tissue rna sequencing RT-qPCR

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long non-coding rna CRALA is associated with poor response to chemotherapy in primary breast cancer

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THORACIC CANCER 2017年第6期8卷 582-591页

作者： Li, Yudong Wang, Baoxiao Lai, Hongna Li, Shunying You, Qiuting Fang, Yichao Li, Qian Liu, Yujie Sun Yat Sen Univ Sun Yat Sen Mem Hosp Guangdong Prov Key Lab Malignant Tumor Epigenet & Guangzhou Guangdong Peoples R China Sun Yat Sen Univ Sun Yat Sen Mem Hosp Breast Tumor Ctr 107 Yanjiang West Rd Guangzhou 510120 Guangdong Peoples R China

BackgroundBreast cancer is the most commonly diagnosed cancer in women, and has become the second leading cause of cancer death among women worldwide. Chemoresistance has become an important problem in breast cancer clinics. The identification of new mechanisms affecting chemosensitivity is of great clinical value for the treatment of breast cancer. MethodsThe expression levels of chemoresistance-associated long non-coding rna (CRALA), a newly discovered long non-coding rna, were measured by quantitative real time-PCR in 79 pre-treatment biopsied primary breast cancer samples. Small interfering rnas were used to knockdown CRALA expression. The effect of CRALA on chemosensitivity was evaluated using cell growth assay. Resultsnon-responding tumors (poor response to chemotherapy, 32 samples) had fourfold higher CRALA expression than responding tumors (good response to chemotherapy, 47 samples). CRALA is upregulated in chemoresistant breast cancer cell lines compared to their parental lines. Silencing of CRALA in chemoresistant breast cancer cells resensitizes the cells to chemotherapy in vitro. Furthermore, univariate and multivariate analysis showed that higher CRALA expression was significantly associated with poor prognosis in 144 breast cancer patients. ConclusionThe study findings indicate that CRALA expression may be an important biomarker for predicting the clinical response to chemotherapy and prognosis in breast cancer patients. It is possible to target CRALA to reverse chemoresistance in breast cancer patients.

关键词： Chemoresistance CRALA long non-coding rna primary breast cancer response to chemotherapy

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long non-coding rna ENST00000503625 is a potential prognostic biomarker and metastasis suppressor gene in prostate cancer

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JOUrnaL OF CANCER RESEARCH AND CLINICAL ONCOLOGY 2023年第10期149卷 7305-7317页

作者： Li, Yaoming Fang, Ziyu Ge, Silun Li, Jingyi Qu, Le Shi, Xiaolei Zhang, Wei Sun, Yinghao Ren, Shancheng Wang, Luofu Army Med Univ Daping Hosp Inst Surg Res Army Med CtrDept Urol Chongqing 400042 Peoples R China Naval Med Univ Changhai Hosp Dept Urol Shanghai 200433 Peoples R China Nanjing Med Univ Jinling Hosp Dept Urol Nanjing 201101 Peoples R China Naval Med Univ Changzheng Hosp Dept Urol Shanghai 200003 Peoples R China

BackgroundDysregulation of long non-coding rnas (lncrnas) emerges to be a hallmark of cancers. Metastatic prostate cancer and localized disease that recurs after treatment are clinical challenges, it remains unclear how lncrna plays a role in those *** previous rna-Seq data on 65 prostate cancer and adjacent normal tissues. We identified a novel lncrna ENST00000503625 down-regulated in prostate cancer and correlated with tumor progression characteristics. Public datasets were examined for associations between ENST00000503625 expression and clinical parameters and prognoses. Subsequently, we constructed and externally validated a nomogram for predicting biochemical recurrence (BCR). Finally, in vitro experiments were carried out to determine how ENST00000503625 functions biologically in prostate *** ENST00000503625 in tumor was associated with poor clinical features and prognoses. TCGA pan-cancer analysis found that ENST00000503625 was deregulated in a variety of tumors and correlated with overall survival, disease-specific survival, and progression-free survival. The nomogram for predicting BCR was constructed using TCGA data, which exhibited excellent accuracy in external validation with Chinese Prostate Cancer Genome and Epigenome Atlas data. Gene Ontology and KEGG pathway analysis found that genes related to ENST00000503625 were enriched in multiple tumor progression related pathways. When ENST00000503625 was knocked down in vitro, the epithelial-mesenchymal transition was induced, by which cancer cells migrated and invaded more *** data suggested that ENST00000503625 may serve as a potential prognostic marker or a therapeutic target for prostate cancer metastases.

关键词： long non-coding rna ENST00000503625 Prostate cancer Prognosis Metastasis

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long non-coding rna DILC regulates liver cancer stem cells via IL-6/STAT3 axis

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JOUrnaL OF HEPATOLOGY 2016年第6期64卷 1283-1294页

作者： Wang, Xue Sun, Wen Shen, Weifeng Xia, Mingyang Chen, Cheng Xiang, Daimin Ning, Beifang Cui, Xiuliang Li, Hengyu Li, Xiaofeng Ding, Jin Wang, Hongyang Second Mil Med Univ Eastern Hepatobiliary Surg Hosp Int Cooperat Lab Signal Transduct 225 Changhai Rd Shanghai 200438 Peoples R China Second Mil Med Univ Eastern Hepatobiliary Surg Hosp Dept Hepat Surg Shanghai 200438 Peoples R China Changzheng Hosp Dept Gastroenterol Shanghai 200003 Peoples R China Natl Ctr Liver Canc Shanghai 201805 Peoples R China

Background & Aims: Emerging evidence has demonstrated the aberrant expression of long non-coding rnas (lncrnas) in various malignancies including HCC. However, the knowledge of cancer stem cell-related lncrnas remains limited. Methods: lnc-DILC (lncrna downregulated in liver cancer stem cells (LCSCs)) was identified by microarray and validated by real-time PCR. The role of lnc-DILC in LCSCs was assessed both in vitro and in vivo. Pull down assay and oligoribonucleotides or oligodeoxynucleotides treatment were conducted to evaluate the interaction between lnc-DILC and interleukin-6 (IL-6) promoter. Results: Depletion of lnc-DILC markedly enhanced LCSC expansion and facilitated HCC initiation and progression, whereas ectopic expression of lnc-DILC dramatically inhibited LCSC expansion. Mechanistically, lnc-DILC inhibited the autocrine IL-6/STAT3 signaling. The putative binding locus of lnc-DILC within IL-6 promoter was confirmed by pull down assay. Consistently, the oligoribonucleotide mimics and an oligodeoxynucleotide decoy of lnc-DILC abrogated the effects on IL-6 transcription, STAT3 activation and LCSC expansion triggered by lnc-DILC depletion and lnc-DILC overexpression. Moreover, our data suggested that lnc-DILC mediated the crosstalk between TNF-alpha/NF-kappa B signaling and IL-6/STAT3 cascade. Clinical investigation demonstrated the reduction of lnc-DILC in patient HCCs, and suggested the correlation between lnc-DILC levels and IL-6, EpCAM or CD24 expression. Decreased lnc-DILC expression in HCCs predicts early recurrence and short survival of patients, highlighting its prognostic value. Conclusions: lnc-DILC mediates the crosstalk between TNF-alpha/NF-kappa B signaling and autocrine IL-6/STAT3 cascade and connects hepatic inflammation with LCSC expansion, suggesting that lnc-DILC could be not only a potential prognostic biomarker, but also a possible therapeutic target against LCSCs. (C) 2016 European Association for the Study of the Liver. Published by Els

关键词： Hepatocellular carcinoma long non-coding rna Liver cancer stem cell Interleukin-6

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long non-coding rna linc00665 inhibits CDKN1C expression by binding to EZH2 and affects cisplatin sensitivity of NSCLC cells

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MOLECULAR THERAPY-NUCLEIC ACIDS 2021年 23卷 1053-1065页

作者： Yang, Daolu Feng, Wenyan Zhuang, Yu Liu, Junxia Feng, Zhenqing Xu, Tianwei Wang, Wei Zhu, Yefei Wang, Zhaoxia Nanjing Med Univ Dept Oncol Affiliated Hosp 2 Nanjing 210011 Peoples R China Nanjing Med Univ Dept Thorac Surg Affiliated Hosp 1 Nanjing 210029 Peoples R China Nanjing Med Univ Key Lab Antibody Tech Natl Hlth Commiss Nanjing 211166 Jiangsu Peoples R China Nanjing Med Univ Lab Med Ctr Affiliated Hosp 2 Nanjing 210011 Peoples R China

long non-coding rnas (lncrnas) can play significant regulatory roles in cells that affect the development and acquired drug resistance of lung cancer. Herein, we report that lncrna linc00665 is significantly upregulated in non-small cell lung cancer (NSCLC) tissues compared with adjacent normal tissues. linc00665 affects the sensitivity of NSCLC cells to the chemotherapy drug cisplatin (DDP), making it a potential target for the treatment of NSCLC. Functional experiments showed that linc00665 enhanced the proliferation and migration of NSCLC cells in vivo and in vitro, and knocking down linc00665 could enhance the drug sensitivity of NSCLC cells to DDP. Further work revealed that linc00665 could recruit enhancer of zeste homolog 2 (EZH2) to the promoter region of cyclin-dependent kinase inhibitor 1C (CDKN1C) to inhibit its transcription and thus carry out its tumorigenic role. In conclusion, our study elucidated the carcinogenic role of the linc00665-EZH2-CDKN1C axis in NSCLC tumors and its ability to influence the sensitivity of these tumors to DDP. These results suggest that linc00665 may be a potential diagnostic marker and therapeutic target in NSCLC, and they also provide a new direction for the development of clinical reversal methods for acquired drug resistance in patients with NSCLC.

关键词： linc00665 CDKN1C long non-coding rna EZH2 non-small cell lung cancer cisplatin drug sensitivity

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long non-coding rna as a novel biomarker and therapeutic target in aggressive B-cell non-Hodgkin lymphoma: A systematic review

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JOUrnaL OF CELLULAR AND MOLECULAR MEDICINE 2023年第14期27卷 1928-1946页

作者： Khanmohammadi, Shaghayegh Fallahtafti, Parisa Univ Tehran Med Sci Res Ctr Immunodeficiencies Pediat Ctr Excellence Childrens Med Ctr Tehran Iran Univ Tehran Med Sci Endocrinol & Metab Populat Sci Inst Noncommun Dis Res Ctr Tehran Iran Univ Tehran Med Sci Sch Med Tehran Iran Univ Tehran Med Sci Sch Med Poorsina St Keshavarz Blvd Tehran Iran

Cancer initiation and progression have been associated with dysregulated long non-coding rna (lncrna) expression. However, the lncrna expression profile in aggressive B-cell non-Hodgkin lymphoma (NHL) has not been comprehensively characterized. This systematic review aims to evaluate the role of lncrnas as a biomarker to investigate their future potential in the diagnosis, real-time measurement of response to therapy and prognosis in aggressive B-cell NHL. We searched PubMed, Web of Science, Embase and Scopus databases using the keywords "long non-coding rna", "Diffuse large B-cell lymphoma", "Burkitt's lymphoma" and "Mantle cell lymphoma". We included studies on human subjects that measured the level of lncrnas in samples from patients with aggressive B-cell NHL. We screened 608 papers, and 51 papers were included. The most studied aggressive B-cell NHL was diffuse large B-cell lymphoma (DLBCL). At least 79 lncrnas were involved in the pathogenesis of aggressive B-cell NHL. Targeting lncrnas could affect cell proliferation, viability, apoptosis, migration and invasion in aggressive B-cell NHL cell lines. Dysregulation of lncrnas had prognostic (e.g. overall survival) and diagnostic values in patients with DLBCL, Burkitt's lymphoma (BL), or mantle cell lymphoma (MCL). Furthermore, dysregulation of lncrnas was associated with response to treatments, such as CHOP-like chemotherapy regimens, in these patients. Lncrnas could be promising biomarkers for the diagnosis, prognosis and response to therapy in patients with aggressive B-cell NHL. Additionally, lncrnas could be potential therapeutic targets for patients with aggressive B-cell NHL like DLBCL, MCL or BL.

关键词： aggressive non-Hodgkin lymphoma biomarker Burkitt's lymphoma diffuse large B-cell lymphoma long non-coding rna mantle cell lymphoma non-Hodgkin lymphomas

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long non-coding rna highly up-regulated in liver cancer promotes epithelial-to-mesenchymal transition process in oral squamous cell carcinoma

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JOUrnaL OF CELLULAR AND MOLECULAR MEDICINE 2019年第4期23卷 2645-2655页

作者： Su, Wen Tang, Jing Wang, Yufan Sun, Shuai Shen, Yuehong Yang, Hongyu Peking Univ Shenzhen Hosp Dept Oral & Maxillofacial Surg Shenzhen Guangdong Peoples R China Anhui Med Univ Peking Univ Shenzhen Hosp Clin Coll Hefei Anhui Peoples R China Jingzhou Cent Hosp Jingzhou Hubei Peoples R China

Oral squamous cell carcinoma (OSCC) is an oral and maxillofacial malignancy that exhibits high incidence worldwide. In diverse human cancers, the long non-coding rna (lncrna) highly up-regulated in liver cancer (HULC) is aberrantly expressed, but how HULC affects OSCC development and progression has remained mostly unknown. We report that HULC was abnormally up-regulated in oral cancer tissues and OSCC cell lines, and that suppression of HULC expression in OSCC cells not only inhibited the proliferation, drug tolerance, migration and invasion of the cancer cells, but also increased their apoptosis rate. Notably, in a mouse xenograft model, HULC depletion reduced tumorigenicity and inhibited the epithelial-to-mesenchymal transition process. Collectively, our findings reveal a crucial role of the lncrna HULC in regulating oral cancer carcinogenesis and tumour progression, and thus suggest that HULC could serve as a novel therapeutic target for OSCC.

关键词： epithelial-to-mesenchymal transition highly up-regulated in liver cancer long non-coding rna oral squamous cell carcinoma

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long non-coding rna FENDRR inhibits the stemenss of colorectal cancer cells through directly binding to Sox2 rna

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BIOENGINEERED 2021年第1期12卷 8698-8708页

作者： Zhao, Xin Wu, Jincheng Li, Yongwen Ye, Feng Wang, Chunyue Xiamen Univ Dept Med Oncol Affiliated Hosp 1 55 Zhenhai Rd Xiamen 361003 Fujian Peoples R China Xiamen Univ Dept Gen Surg Affiliated Hosp 1 Xiamen Fujian Peoples R China Xiamen Univ Dept Gastrointestinal Surg Affiliated Hosp 1 Xiamen Fujian Peoples R China

Cancer stem cells (CSCs) contribute to malignant features. long non-coding rna (Lncrna) FENDRR has been shown to regulate tumor proliferation, migration, and invasion. However, the effects of FENDRR on the CSC-like traits of colorectal cancer cells remain to be elucidated. Here, we identified that lncrna FENDRR level was remarkably lower in spheres formed by colorectal cancer cells compared to that in parental cancer cells. Further functional experiments showed that FENDRR overexpression attenuated the CSC-like traits of colorectal cancer spheres, while FENDRR knockdown conferred the CSC-like traits for colorectal cancer cells, as characterized by the alteration of ALDH activity, sphere-formation ability, and expression of stemness markers (Oct4, Sox2, and KLF4). rna-rna interaction in vitro analysis combined with mrna stability assay revealed that lncrna FENDRR directly interacted with Sox2 mrna 3'UTR, reduced its mrna stability and thus inhibited Sox2 expression. In addition, lncrna FENDRR-mediated effects on the CSC-like traits of colorectal cancer cells depended on Sox2 expression. This work suggests that lncrna FENDRR can block the CSC-like traits in colorectal cancer cells through directly interacting with Sox2 mrna 3'UTR.

关键词： long non-coding rna sox2 cancer stem cell mrna stability rna-rna interaction

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long non-coding rna THOR promotes human osteosarcoma cell growth in vitro and in vivo

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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 2018年第4期499卷 913-919页

作者： Chen, Wangzhen Chen, Meikai Xu, Yifan Chen, Xuerong Zhou, Ping Zhao, Xiaofeng Pang, Fei Liang, Wenqing Zhejiang Univ Shaoxing Hosp Shaoxing Peoples Hosp Dept Orthopaed 568 Zhongxing North Rd Shaoxing 312000 Peoples R China

long non-coding rna (Lncrna) dysregulation is associated with human osteosarcoma (OS) cell progression. Recent studies have characterized a novel but ultra-conserved Lncrna THOR ("Lnc-THOR") as a cancer-specific Lncrna, mediating cell growth. In the current study, we show that Lnc-THOR is expressed in established and primary human OS cells. It is also detected in human OS tissues, but not in the surrounding normal bone tissues. sirna-induced knockdown or CRSIPR/Cas9-mediated knockout Lnc-THOR significantly inhibited human OS cell survival and proliferation. Insulin-like growth factor 2 mrna-binding protein 1 (1GF2BP1) target mrnas, including IGF2, GLI1 and CD44, were downregulated in Lnc-THOR-silenced OS cells as well. Conversely, forced over-expression of Lnc-THOR enhanced IGF2BP1 target mrna expression, promoting OS cell survival and proliferation. In vivo, xenograft tumors of Lnc-THOR-knockout U2OS cells grew significantly slower than the control U2OS tumors. Together, these results show that Lnc-THOR expression is essential for human OS cell growth. Lnc-THOR could be a novel therapeutic target and/or diagnosis marker for human OS. (C) 2018 Elsevier Inc. All rights reserved.

关键词： Osteosarcoma long non-coding rna Lnc-THOR IGF2BP1 Cell growth

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long non-coding rna expressed in macrophage co-varies with the inflammatory phenotype during macrophage development and polarization

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JOUrnaL OF CELLULAR AND MOLECULAR MEDICINE 2019年第10期23卷 6530-6542页

作者： Xie, Yixin Wang, Min Tian, Jingjing Li, Xianping Yang, Min Zhang, Kan Tan, Shan Luo, Lingli Luo, Can Peng, longkai Tang, Aiguo Cent South Univ Dept Lab Med Xiangya Hosp 2 Changsha Hunan Peoples R China Cent South Univ Dept Urol Organ Transplantat Xiangya Hosp 2 Ctr Organ Transplantat Changsha Hunan Peoples R China

Advances in microarray, rna-seq and omics techniques, thousands of long non-coding rnas (lncrnas) with unknown functions have been discovered. Lncrnas have presented a diverse perspective on gene regulation in diverse biological processes, especially in human immune response. Macrophages participate in the whole phase of immune inflammatory response. They are able to shape their phenotype and arouse extensive functional activation after receiving physiological and pathological stimuli. Emerging studies indicated that lncrnas participated in the gene regulatory network during complex biological processes of macrophage, including macrophage-induced inflammatory responses. Here, we reviewed the existing knowledges of lncrnas in the processes of macrophage development and polarization, and their roles in several different inflammatory diseases. Specifically, we focused on how lncrnas function in macrophage, which might help to discover some potential therapeutic targets and diagnostic biomarkers.

关键词： cancer immune response inflammation long non-coding rna macrophage polarization

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