• Bibliometric analysis
• Colorectal cancer
• Knowledge map
• Long noncoding RNA

• acute myeloid leukemia
• apoptosis
• cell cycle
• hesperidin

• Cancer
• Long non-coding RNA CASC15
• Meta-analysis
• Prognosis
• TCGA

• ORF
• function
• gastrointestinal cancer
• long non-coding RNA (lncRNA)
• small peptide

• National Natural Science Foundation of China

• HOTTIP
• colorectal cancer
• rs1859168

• colon adenocarcinoma
• colorectal cancer
• epigenetic
• long noncoding RNAs
• microRNA

• Cancer
• HOTTIP
• HOXA transcript at the distal tip
• lncRNA

• Animals
• Biomarkers, Tumor/genetics
• Gene Expression Regulation, Neoplastic
• Humans
• Intracellular Signaling Peptides and Proteins/metabolism
• Neoplasms/genetics
• Neoplasms/pathology
• RNA, Long Noncoding/genetics

Several studies have indicated that HOXA transcript at the distal tip (HOTTIP) play important roles in the tumorigenesis and development of various cancers. We aim to investigate the expression and prognostic value of HOTTIP in clear cell renal cell carcinoma (ccRCC). A systematic review of PubMed, Embase, Medline, and Web of Science databases was performed to select eligible literatures relevant to the correlation between HOTTIP expression and clinical outcome of different cancers. The association between the HOTTIP level and overall survival (OS), lymph node metastasis (LNM), or clinical stage was subsequently analyzed. Survival analyses were performed in a large cohort of more than 500 patients with ccRCC from The Cancer Genome Atlas (TCGA) using bioinformatic methods. Seventeen studies with a total of 1594 patients with thirteen kinds of carcinomas were included in this analysis. The result showed that high HOTTIP expression could predict worse outcome in cancer patients, with the pooled hazard ratio (HR) of 2.34 (95% confidence interval (CI) 1.96–2.79, p < 0.0001). The result also showed that elevated HOTTIP expression was correlated with more LNM (OR = 2.61, 95% CI 1.91-3.58, p < 0.0001) and advanced clinical stage (OR = 3.57, 95% CI 2.58-4.93, p < 0.0001). We further validated that ccRCC patients with higher HOTTIP expression tend to have unsatisfactory outcomes both in the entire TCGA dataset and different clinical stratums, like age, grade, and stage. The tumor of those patients was associated with a larger size, easier to metastasis, advanced clinical stage, and a higher pathological grade. These findings suggested that increased HOTTIP expression might act as a novel prognostic marker for ccRCC patients.

• HOTTIP
• HOTTIP–WDR5–MLL1–H3K4me3
• HOXA13
• Pancreatic cancer
• miR–497

• Carcinoma, Pancreatic Ductal/genetics
• Carcinoma, Pancreatic Ductal/pathology
• Cell Proliferation
• Gene Expression Regulation, Neoplastic
• Histone-Lysine N-Methyltransferase/genetics
• Histone-Lysine N-Methyltransferase/metabolism
• Homeodomain Proteins/genetics
• Homeodomain Proteins/metabolism
• Humans
• Intracellular Signaling Peptides and Proteins/genetics
• Intracellular Signaling Peptides and Proteins/metabolism
• MicroRNAs/genetics
• Myeloid-Lymphoid Leukemia Protein/genetics
• Myeloid-Lymphoid Leukemia Protein/metabolism
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/pathology
• RNA, Long Noncoding/genetics
• Transcriptional Activation
• Up-Regulation
• Pancreatic Neoplasms

• HOTAIR
• epigenetics
• lncRNA
• mechanosensitive
• miRNA
• shear stress

• HOXA transcript at the distal tip
• In situ hybridization
• Long noncoding RNA
• Prostate cancer

• Biomarker
• Circulating long non-coding RNAs
• Colorectal adenoma
• Colorectal cancer
• Diagnostic marker
• Exosome
• Long non-coding RNA
• Prognostic marker

• Biomarkers, Tumor/blood
• Biomarkers, Tumor/isolation & purification
• Biomarkers, Tumor/metabolism
• Biopsy
• Carcinogenesis/genetics
• Cell-Free Nucleic Acids/blood
• Cell-Free Nucleic Acids/isolation & purification
• Colon/pathology
• Colorectal Neoplasms/blood
• Colorectal Neoplasms/diagnosis
• Colorectal Neoplasms/mortality
• Disease Progression
• Disease-Free Survival
• Gene Expression Regulation, Neoplastic
• Humans
• Neoplasm Staging
• Prognosis
• RNA, Long Noncoding/blood
• RNA, Long Noncoding/isolation & purification
• RNA, Long Noncoding/metabolism
• Rectum/pathology

• Exosomes
• colorectal cancer
• diagnosis
• liquid biopsy
• long non-coding RNA

Background: The role of long non-coding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP) as an oncogene in varieties of human cancer including colorectal cancer (CRC) has been extensively researched. The expression and function of lncRNAs could be affected by single nucleotide polymorphisms (SNPs), which are associated with cancer susceptibility and prognosis. However, no investigation has focused on the association between HOTTIP SNPs and CRC. The aim of the present study was to explore the association of polymorphisms in the lncRNA HOTTIP gene with CRC risk and prognosis. Methods: A total of 1848 subjects were enrolled in our study, including 884 CRC cases and 964 controls. Genotyping for five HOTTIP tagSNPs (rs3807598, rs17501292, rs2067087, rs17427960, and rs78248039) was performed by applying Kompetitive allele specific PCR (KASP). Results: The results showed three SNPs (rs3807598, rs2067087, and rs17427960) were associated with enhanced CRC risk both in overall and stratified analysis. One polymorphism, rs17501292, could improve the overall survival (OS) of CRC patients in the tumor of ulcerative/invasive-type subgroup. Conclusion: These findings suggest HOTTIP SNPs could potentially be predictive biomarkers for CRC risk and prognosis. The present study provides clues for further exploration of novel lncRNA-based genetic biomarkers to predict CRC susceptibility as well as clinical outcome.

• HOTTIP
• colorectal cancer
• polymorphism
• prognosis
• susceptibility

• Epigenetic alteration
• Metastasis
• Microbiota meditation
• Targeted therapy design
• Tumor proliferation
• lncRNA
• miRNA

• HOTTIP
• PVT1
• UCA1
• biomarker
• colorectal cancer
• lymph node metastasis

Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides with limited coding potential, which have emerged as novel regulators in many biological and pathological processes, including growth, development, and oncogenesis. Accumulating evidence suggests that lncRNAs have a special role in the osteogenic differentiation of various types of cell, including stem cells from different sources such as embryo, bone marrow, adipose tissue and periodontal ligaments, and induced pluripotent stem cells. Involved in complex mechanisms, lncRNAs regulate osteogenic markers and key regulators and pathways in osteogenic differentiation. In this review, we provide insights into the functions and molecular mechanisms of lncRNAs in osteogenesis and highlight their emerging roles and clinical value in regenerative medicine and osteogenesis-related diseases.

Cite this article: J. Zhang, X. Hao, M. Yin, T. Xu, F. Guo. Long non-coding RNA in osteogenesis: A new world to be explored. Bone Joint Res 2019;8:73–80. DOI: 10.1302/2046-3758.82.BJR-2018-0074.R1.

• Molecular mechanism
• Osteogenesis
• Osteogenic differentiation
• lncRNA

• HOTTIP
• apoptosis
• metastasis
• oral tongue squamous cell carcinoma
• proliferation
• tumorigenicity

Colorectal cancer (CRC) is the 3^rd most common malignancies worldwide. Metastasis is responsible for more than 90% CRC patients' death. Long noncoding RNAs (lncRNAs) are an important class of transcribed RNA molecules greater than 200 nucleotides in length. With the development of whole genome sequencing technologies, they have been gained more attention. Accumulating evidences suggest that abnormal expression of lncRNAs in diverse diseases are involved in various biological functions such as proliferation, apoptosis, metastasis and differentiation by acting as epigenetic, splicing, transcriptional or post-transcriptional regulators. Aberrant expression of lncRNAs has also been found in CRC. Besides, recent studies have indicated that lncRNAs play important roles in tumourigenesis and cancer metastasis. They participate in the process of metastasis by activing or inhibiting the metastatic pathways. However, their functions on the development of cancer metastasis are poorly understood. In this review, we highlight the findings of roles for lncRNAs in CRC metastasis and review the metastatic pathways of lncRNAs leading to cancer metastasis in CRC, including escape of apoptosis, epithelial-mesenchymal transition (EMT), angiogenesis and invasion, migration and proliferation. Furthermore, we also discuss the potential clinical application of lncRNAs in CRC as diagnostic markers and therapeutic targets.

• colorectal cancer
• lncRNAs
• metastasis
• review

Studies of long non-coding RNAs (lncRNAs) have been prevalent in the field of non-coding RNA regulation in recent years. LncRNAs exert crucial effects on malignant cell processes in the gastrointestinal system, including proliferation. Aberrant lncRNA expression, through both oncogenes and tumor suppressor genes, is instrumental to tumor cell proliferation. Here, we summarize the different molecular mechanisms and relevant signaling pathways through which multifarious lncRNAs regulate cell proliferation and we show that lncRNAs are potential biomarkers for gastrointestinal cancers.

Abnormal expression of long non-coding RNA (lncRNAs) often facilitates unrestricted growth of cancer cells. Long intergenic non-protein coding RNA 1510, an enhancer lncRNA (LINC01510), a lncRNA enhancer is upregulated in colorectal cancer (CRC), and its expression might relate to MET as revealed by lncRNA microarray data. However, the potential biological role of LINC01510 and its regulatory mechanism in CRC remain unclear. Therefore, we investigated the involvement of LINC01510 in the proliferation of CRC cells.

Microarray analysis, In situ hybridization, colony formation assay, MTT assay, Western blotting, quantitative RT-PCR and flow cytometry were applied. The two-tailed Student’s t test and analysis of variance or general linear model of single factor variable was used for statistical analyse.

In the present study, we found that LINC01510 was significantly upregulated in CRC tissues and cell lines. The LINC01510 expression level were associated with the clinicopathological grade and stage. Meanwhile, gain- and loss-of-function assays demonstrated that LINC01510 overexpression increased CRC cell proliferation, and promoted cell cycle progression from the G1 phase to the S phase. Further study indicated that LINC01510 was positively correlated with the expression of MET, and its effects were most likely at the transcriptional level.

Taken together, our findings suggested that upregulation of LINC01510 contributes to the proliferation of CRC cells, at least in part, through the regulation of MET protein. LINC01510 could be a candidate prognostic biomarker and a target for new therapies in CRC patients.

• Cell cycle
• Cell growth
• Colorectal cancer
• LINC01510
• Long non coding RNA
• MET

Whole-transcriptome analyses have revealed that a large proportion of the human genome is transcribed in non-protein-coding transcripts, designated as long non-coding RNAs (lncRNAs). Rather than being “transcriptional noise”, increasing evidence indicates that lncRNAs are key players in the regulation of many biological processes, including transcription, post-translational modification and inhibition and chromatin remodeling. Indeed, lncRNAs are widely dysregulated in human cancers, including hepatocellular carcinoma (HCC). Functional studies are beginning to provide insights into the role of oncogenic and tumor suppressive lncRNAs in the regulation of cell proliferation and motility, as well as oncogenic and metastatic potential in HCC. A better understanding of the molecular mechanisms and the complex network of interactions in which lncRNAs are involved could reveal novel diagnostic and prognostic biomarkers. Crucially, it may provide novel therapeutic opportunities to add to the currently limited number of therapeutic options for HCC patients. In this review, we summarize the current status of the field, with a focus on the best characterized dysregulated lncRNAs in HCC.

• carcinogenesis
• hepatocellular carcinoma
• liver cancer
• long non-coding RNA

Long noncoding RNA HOTTIP plays important roles in the generation and progression of human cancers. Exosomes participate in cellular communication by transmitting moleculars between cells and are regarded as suitable candidates for non-invasive diagnosis. However, the existence of HOTTIP in the circulating exosomes and the potential roles of exosomal HOTTIP in gastric cancer (GC) was poorly understood. This study aims at investigating the clinical roles of exosomal HOTTIP in GC. Serum exosomal HOTTIP from 246 subjects (126 GC patients and 120 healthy people) were detected by reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR). Our results showed that expression levels of exosomal HOTTIP were typically upregulated in GC than in normal control (P < 0.001). And its expression levels were significantly correlated with invasion depth (P = 0.0298) and TNM stage (P < 0.001). The AUC for exosomal HOTTIP was 0.827, which demonstrated a higher diagnostic capability than CEA, CA 19–9 and CA72–4 (AUC = 0.653, 0.685 and 0.639, respectively) (P < 0.001). The Kaplan–Meier analysis showed a correlation between increased exosomal HOTTIP levels and poor overall survival (OS) (logrank P < 0.001). And univariate and multivariate COX analysis revealed exosomal HOTTIP overexpression was an independent prognostic factor in GC patients (P = 0.027). These findings demonstrated that exosomal HOTTIP may be a potential biomarker for GC in diagnosis and prognosis.

• Diagnosis
• Gastric cancer
• HOTTIP
• Long noncoding RNA
• Prognosis

• CRNDE
• human cancer
• lncRNA
• prognosis

Colorectal cancer (CRC) is a common gastrointestinal cancer, with a high incidence and high mortality. Long non-coding RNAs (lncRNAs) are involved in the development, invasion and metastasis, early diagnosis, prognosis, the chemoresistance and radioresistance of CRC through interference with mRNA activity, directly combining with proteins to regulate their activity or alter their localization, influencing downstream gene expression by inhibiting RNA polymerase and regulating gene expression as competing endogenous RNAs. Recent progress in next generation sequencing and transcriptome analysis has revealed that tissue and cancer-type specific lncRNAs could be useful prognostic markers. Here, the CRC-associated lncRNAs from recent studies until October 2016 are reviewed and multiple studies that have confirmed CRC-associated lncRNAs are summarized. This review may be helpful in understanding the overall relationships between the lncRNAs involved in CRC.

• colorectal cancer
• epithelial-mesenchymal transition
• invasion
• long non-coding RNAs

• BANCR
• Colorectal cancer
• Lymph node metastasis
• Prognosis
• lncRNA

Long non-coding RNA (lncRNA) is emerging as an critical regulator in multiple cancers, including pancreatic cancer (PC). Recently, lncRNA SNHG15 was found to be up-regulated in gastric cancer and hepatocellular carcinoma, exerting oncogenic effects. Nevertheless, the biological function and regulatory mechanism of SNHG15 remain unclear in pancreatic cancer (PC). In this study, we reported that SNHG15 expression was also upregulated in PC tissues, and its overexpression was remarkably associated with tumor size, tumor node metastasis (TNM) stage and lymph node metastasis in patients with PC. SNHG15 knockdown inhibited proliferative capacities and suppressed apoptotic rate of PC cells in vitro, and impaired in-vivo tumorigenicity. Additionally, RNA immunoprecipitation (RIP) assays showed that SNHG15 epigenetically repressed the P15 and Kruppel-like factor 2 (KLF2) expression via binding to enhancer of zeste homolog 2 (EZH2), and chromatin immunoprecipitation assays (CHIP) assays demonstrated that EZH2 was capable of binding to promoter regions of P15 and KLF2 to induce histone H3 lysine 27 trimethylation (H3K27me3). Furthermore, rescue experiments indicated that SNHG15 oncogenic function partially involved P15 and KLF2 repression. Consistently, an inverse correlation between the expression of SNHG15 and traget genes were found in PC tissues. Our results reported that SNHG15 could act as an oncogene in PC, revealing its potential value as a biomarker for early detection and individualized therapy.

• P15 and KLF2
• SNHG15
• long noncoding RNA
• pancreatic cancer
• proliferation

• Colorectal cancer
• Expression profiling
• Long non-coding RNA
• Protein–protein interaction analysis

Evidence indicates that long non-coding RNAs (lncRNAs) play a critical role in the regulation of tumor cellular processes, such as proliferation, apoptosis, and metastasis. LncRNA CRNDE (Colorectal Neoplasia Differentially Expressed) is located at human chromosome 16 and has been found overexpressed in a variety of cancers including colorectal cancer (CRC). In this paper, we report that lncRNA CRNDE expression was remarkably upregulated in CRC tissues and that lncRNA CRNDE overexpression was positively correlated with advanced pathological stages and larger tumor sizes. In addition, the knockdown of CRNDE significantly suppressed proliferation and caused apoptosis of CRC cells both in vitro and in vivo. Furthermore, RNA immunoprecipitation and chromatin immunoprecipitation assays demonstrated that lncRNA CRNDE could epigenetically suppress the expressions of dual-specificity phosphatase 5 (DUSP5) and CDKN1A by binding to EZH2 (the key components of Polycomb repressive complex 2 (PRC2)), thus promoting CRC development. In conclusion, our data suggest that the lncRNA CRNDE promotes the progression of CRC and is a potential therapeutic target for CRC intervention.

The prognosis of colorectal carcinoma (CRC) is unstable in the stage II-III patients. Patients with early stage II CRC have a relative poor prognosis while other stage III CRC patients have a better prognosis. In our work, by utilizing the expression of lncRNAs and mRNAs measured by microarray (GSE39582), we constructed a risk score staging system with Cox multivariate regression model to predict the outcome of grade II-III CRC patients. Ten genes including two lncRNAs and eight mRNAs were used to estimate the survival of stage II-III CRC patients. The patients with high risk scores have poorer survival rate those with low risk scores, significantly. These results were further validated in another three independent datasets (GSE37892, GSE33113, and GSE17536). The relationship between clinical information and were evaluated, and the risk score is independent from the other clinical information and performs better in evaluating the survival of stage II-III CRC patients. Moreover, the correlation between chemotherapy was also evaluated, and we found that both patients with or without chemotherapy have a poor survival in high risk group. Gene Set Enrichment Analysis were used to find the difference between high-risk and low-risk groups, and pathways including cell adhesion and focal adhesion were significantly enriched, suggesting that the risk score reflects the status of cell-cell physical interaction. In summary, we constructed a risk staging model for grade II-III CRC, which is independent from and performs better than clinical information.

• Adult
• Age Factors
• Aged
• Aged, 80 and over
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/mortality
• Colorectal Neoplasms/pathology
• Female
• Humans
• Male
• Middle Aged
• Neoplasm Staging
• Prognosis
• RNA, Long Noncoding
• Risk Assessment
• Sex Factors
• Survival Rate

Recently, substantial evidence has demonstrated that pseudogene derived lncRNAs are crucial regulators of cancer development and progression. DUXAP10,a pseudogene derived long non-coding RNA(lncRNA), is overexpression in colorectal cancer (CRC), but its expression pattern, biological function and underlying mechanism in CRC is still undetermined. In this study, we observed that DUXAP10 was up-regulated in CRC tissues which was positively correlated with advanced pathological stages, larger tumor sizes and lymph node metastasis. Additionally, knockdown of DUXAP10 inhibited cell proliferation, induced cell apoptosis and increase the number of G0/G1 cells significantly in the HCT116 and SW480 cell lines. Moreover, DUXAP10 silencing inhibited tumor growth in vivo. Further mechanism study showed that, by binding to histone demethylase lysine-specific demethylase 1 (LSD1), DUXAP10 promote CRC cell growth and reduced cell apoptosis through silencing the expression of p21 and phosphatase and tensin homolog (PTEN) tumor suppressor. Our findings suggested that the pseudogene-derived from lncRNA DUXAP10 promotes the biological progression of CRC and is likely to be a potential therapeutic target for CRC intervention.

• HOTTIP
• Meta-analysis
• Metastasis
• Neoplasms
• Prognosis

• KLF2
• LL22NC03-N64E9.1
• colorectal cancer
• lncRNA
• proliferation

• Colorectal cancer (CRC)
• Long non-coding RNA (lncRNA)
• MicroRNA (miRNA)
• Non-coding RNAs (ncRNAs)
• Signaling pathway

Human Homeobox A transcript at the distal tip (HOTTIP) is a putative oncogene in solid tumors. We performed a meta-analysis to investigate the association between HOTTIP expression and clinical outcomes in cancer patients. Eligible studies were collected from a literature search of the online electronic databases of Embase, Web of Science, PubMed and the China National Knowledge Infrastructure (up to January 2, 2017). Fixed-effects models were used to compute pooled odds ratios (ORs) and hazard ratios (HRs). In total, we analyzed nine studies that included 800 patients with seven tumor types. Overall survival was lower for patients with high HOTTIP expression than for those with low expression (HR = 2.30, 95% confidence interval [CI]: 1.81–2.91, P < 0.001). High HOTTIP expression was also associated with lymph node metastasis (OR = 2.40, 95% CI: 1.70–3.37, P < 0.001), distant metastasis (OR = 3.30, 95% CI: 1.78–6.12, P < 0.001), poor tumor differentiation (OR = 1.55, 95% CI: 1.03–2.32, P = 0.036) and a poor clinical stage (OR = 3.28, 95% CI: 2.22–4.83, P < 0.001). This meta-analysis demonstrated that high HOTTIP expression in cancer patients is associated with poor clinical outcomes. Thus, HOTTIP is a potential predictive biomarker of cancer.

• HOTTIP
• cancer
• clinical outcome
• lncRNA
• meta-analysis

Previously thought of as junk transcripts and pseudogene remnants, long non-coding RNAs (lncRNAs) have come into their own over the last decade as an essential component of cellular activity, regulating a plethora of functions within multicellular organisms. lncRNAs are now known to participate in development, cellular homeostasis, immunological processes, and the development of disease. With the advent of next generation sequencing technology, hundreds of thousands of lncRNAs have been identified. However, movement beyond mere discovery to the understanding of molecular processes has been stymied by the complicated genomic structure, tissue-restricted expression, and diverse regulatory roles lncRNAs play. In this review, we will focus on lncRNAs involved in lung cancer, the most common cause of cancer-related death in the United States and worldwide. We will summarize their various methods of discovery, provide consensus rankings of deregulated lncRNAs in lung cancer, and describe in detail the limited functional analysis that has been undertaken so far.

• LncRNA biology
• RNA biology
• cancer
• lung adenocarcinoma
• transcriptomic analysis

• HOTTIP
• cancer
• lncRNA
• lymph node metastasis
• prognosis

• Biomarkers, Tumor/genetics
• Humans
• Lymphatic Metastasis/genetics
• Lymphatic Metastasis/pathology
• Neoplasms/genetics
• Neoplasms/mortality
• Neoplasms/pathology
• Prognosis
• RNA, Long Noncoding/biosynthesis

The first report of potential mechanisms of IncRNA SNHG17 in CRC, prompting the development of IncRNA-directed diagnosis and treatments.

• FOXP4-AS1
• TNM stage
• apoptosis
• colorectal cancer
• lncRNA
• proliferation

• Apoptosis
• EZH2
• IRAIN
• LSD1
• Pancreatic cancer
• lncRNA

• Apoptosis/genetics
• Cell Line, Tumor
• Cell Proliferation/genetics
• Cyclin-Dependent Kinase Inhibitor p15/biosynthesis
• Cyclin-Dependent Kinase Inhibitor p15/genetics
• Enhancer of Zeste Homolog 2 Protein/metabolism
• Female
• Histone Demethylases/metabolism
• Humans
• Kruppel-Like Transcription Factors/biosynthesis
• Kruppel-Like Transcription Factors/genetics
• Lymphatic Metastasis/genetics
• Male
• Middle Aged
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/pathology
• RNA Interference
• RNA, Long Noncoding/genetics
• RNA, Long Noncoding/metabolism
• RNA, Small Interfering/genetics
• RNA-Binding Proteins/metabolism

• biomarker
• colorectal cancer
• long non-coding RNA
• ncRNA
• prognostic marker

We focus on the current knowledge of HOTTIP in various cancers and illustrate the corresponding mechanism and biological function of HOTTIP during tumor development.