• CSPG4P12
• colorectal cancer
• genetic variant
• susceptibility

• Humans
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/epidemiology
• Male
• Female
• Case-Control Studies
• Polymorphism, Single Nucleotide
• Middle Aged
• Genetic Predisposition to Disease
• Chondroitin Sulfate Proteoglycans/genetics
• Aged
• Risk Factors
• Membrane Proteins

• Biomarkers
• Cancers
• Diagnosis
• MiRNAs
• Pseudogene_derived LncRNA

• Humans
• MicroRNAs/genetics
• RNA, Long Noncoding/genetics
• Pseudogenes/genetics
• Neoplasms/diagnosis
• Neoplasms/genetics
• Prognosis
• Biomarkers, Tumor/genetics

• CTNNA1
• tumorigenesis
• α-catenin

Pseudogenes have been considered as non-functional genes. However, peptides and long non-coding RNAs produced by pseudogenes are expressed in different tumors. Moreover, the dysregulation of pseudogenes is associated with cancer, and their expressions are higher in tumors compared to normal tissues. Recent studies show that pseudogenes can influence the liquid phase condensates formation. Liquid phase separation involves regulating different epigenetic stages, including transcription, chromatin organization, 3D DNA structure, splicing, and post-transcription modifications like m⁶A. Several membrane-less organelles, formed through the liquid phase separate, are also involved in the epigenetic regulation, and their defects are associated with cancer development. However, the association between pseudogenes and liquid phase separation remains unrevealed. The current study sought to investigate the relationship between pseudogenes and liquid phase separation in cancer development, as well as their therapeutic implications.

• National Natural Science Foundation of China

• Circular RNAs
• colorectal cancer
• competing endogenous RNAs
• long non-coding RNAs
• pseudogenes

• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/therapy
• Gene Expression Regulation, Neoplastic
• Gene Regulatory Networks
• Humans
• MicroRNAs/genetics
• MicroRNAs/metabolism
• RNA, Circular/genetics
• RNA, Long Noncoding/genetics
• RNA, Messenger/genetics
• RNA, Messenger/metabolism

• clinicopathological characteristics
• colon cancer
• nomogram
• overall survival
• prognostic genes

Retroposition is RNA-based gene duplication leading to the creation of single exon nonfunctional copies. Nevertheless, over time, many of these duplicates acquire transcriptional capabilities. In human in most cases, these so-called retrogenes do not code for proteins but function as regulatory long noncoding RNAs (lncRNAs). The mechanisms by which they can regulate other genes include microRNA sponging, modulation of alternative splicing, epigenetic regulation and competition for stabilizing factors, among others. Here, we summarize recent findings related to lncRNAs originating from retrocopies that are involved in human diseases such as cancer and neurodegenerative, mental or cardiovascular disorders. Special attention is given to retrocopies that regulate their progenitors or host genes. Presented evidence from the literature and our bioinformatics analyses demonstrates that these retrocopies, often described as unimportant pseudogenes, are significant players in the cell’s molecular machinery.

• disease
• host gene
• lncRNA
• parental gene
• regulation
• retrocopies
• retroposition

• Animals
• Disease/genetics
• Humans
• Neurodegenerative Diseases/genetics
• Open Reading Frames/genetics
• RNA, Long Noncoding/genetics
• RNA, Long Noncoding/metabolism
• Retroelements/genetics

Long non-coding RNAs (lncRNAs) are the most heterogeneous class of non-protein-coding RNAs involved in a broad spectrum of molecular mechanisms controlling genome function, including the generation of complex networks of RNA-RNA competitive interactions. Accordingly, their dysregulation contributes to the onset of many tumors, including colorectal cancer (CRC). Through a combination of in silico approaches (statistical screening of expression datasets) and in vitro analyses (enforced expression, artificial inhibition, or activation of pathways), we identified LINC00483 as a potential tumor suppressor lncRNA in CRC. LINC00483 was downregulated in CRC biopsies and metastases and its decreased levels were associated with severe clinical features. Inhibition of the MAPK pathway and cell cycle arrest by starvation induced an upregulation of LINC00483, while the epithelial to mesenchymal transition activation by TGFβ-1 and IL-6 caused its down-modulation. Moreover, enforced expression of LINC00483 provoked a slowing down of cell migration rate without affecting cell proliferation. Since LINC00483 was predominantly cytoplasmic, we hypothesized a “miRNA sponge” role for it. Accordingly, we computationally reconstructed the LINC00483/miRNA/mRNA axes and evaluated the expression of mRNAs in different experimental conditions inducing LINC00483 alteration. By this approach, we identified a set of mRNAs sharing the miRNA response elements with LINC00483 and modulated in accordance with it. Moreover, we found that LINC00483 is potentially under negative control of transcription factor HNF4α. In conclusion, we propose that LINC00483 is a tumor suppressor in CRC that, through an RNA-RNA network, may control cell migration and participate in proliferation signaling.

• HNF4α
• IL-6
• TGFβ-1
• colorectal cancer
• competing endogenous RNA
• epithelial–mesenchymal transition
• long non-coding RNAs
• microRNAs

This review summarizes the knowledge about retrogenes in the context of cancer and evolution. The retroposition, in which the processed mRNA from parental genes undergoes reverse transcription and the resulting cDNA is integrated back into the genome, results in additional copies of existing genes. Despite the initial misconception, retroposition-derived copies can become functional, and due to their role in the molecular evolution of genomes, they have been named the “seeds of evolution”. It is convincing that retrogenes, as important elements involved in the evolution of species, also take part in the evolution of neoplastic tumors at the cell and species levels. The occurrence of specific “resistance mechanisms” to neoplastic transformation in some species has been noted. This phenomenon has been related to additional gene copies, including retrogenes. In addition, the role of retrogenes in the evolution of tumors has been described. Retrogene expression correlates with the occurrence of specific cancer subtypes, their stages, and their response to therapy. Phylogenetic insights into retrogenes show that most cancer-related retrocopies arose in the lineage of primates, and the number of identified cancer-related retrogenes demonstrates that these duplicates are quite important players in human carcinogenesis.

• cancer
• retrogenes
• retroposition
• species evolution
• tumor evolution

• Biomarker
• Human cancer
• Pseudogene
• Therapeutic target

Bladder cancer (BLCA) is an urogenital system tumor with a high morbidity. We aimed to explore the function and potential mechanism of α-E-catenin (CTNNA1) in BLCA.

The CTNNA1 expression in BLCA tissues was detected using qRT-PCR and immunohistochemistry. QRT-PCR and Western blot were performed to measure the CTNNA1 expression in BLCA cell lines. CTNNA1 expression was up-regulated in T24 and UMUC-2 cells by CTNNA1 overexpression plasmid transfection. Cell proliferation, apoptosis, migration and invasion were respectively assessed by CCK-8 assay, flow cytometry, wound healing assay and transwell assay. The expression levels of epithelial–mesenchymal transition (EMT)-related factors were tested by qRT-PCR and Western blot. BLCA nude mice models were constructed to explore the effects of CTNNA1 on BLCA in vivo. Gene set enrichment analysis (GSEA) was proceeded to identify the CTNNA1-related pathways in BLCA.

The expressions of CTNNA1 were down-regulated in BLCA tissues and cell lines, and its low expression indicated poor prognosis of BLCA patients. CTNNA1 inhibited cell proliferation, migration, invasion and EMT and promoted cell apoptosis in BLCA cells. CTNNA1 enhanced E-cadherin expression and suppressed N-cadherin, snail, MMP2 and MMP9 expressions in BLCA cells, which suggested that CTNNA1 repressed EMT in BLCA cells. Moreover, CTNNA1 could inhibit tumor growth in vivo. CTNNA1 was positively associated with P53 and apoptosis pathways in BLCA cells.

CTNNA1 inhibited cell proliferation, migration, invasion and EMT and promoted cell apoptosis in BLCA via activating P53 and apoptosis pathways. CTNNA1 might be a novel target in BLCA therapy.

• CTNNA1
• GSEA
• bladder cancer
• cell proliferation
• in vivo study

• apoptosis
• colorectal cancer
• lncRNA CCAT1
• miR-181a-5p
• proliferation

• Adherens junction
• Cancer
• Claudins
• E-cadherin
• Occludin
• Tight junctions

Pseudogenes, abundant in the human genome, are traditionally considered as non-functional “junk genes.” However, recent studies have revealed that pseudogenes act as key regulators at DNA, RNA or protein level in diverse human disorders (including cancer), among which pseudogene-derived long non-coding RNA (lncRNA) transcripts are extensively investigated and has been reported to be frequently dysregulated in various types of human cancer. Growing evidence demonstrates that pseudogene-derived lncRNAs play important roles in cancer initiation and progression by serving as competing endogenous RNAs (ceRNAs) through competitively binding to shared microRNAs (miRNAs), thus affecting both their cognate genes and unrelated genes. Herein, we retrospect those current findings about expression, functions and potential ceRNA mechanisms of pseudogene-derived lncRNAs in human cancer, which may provide us with some crucial clues in developing potential targets for cancer therapy in the future.

• cancer
• circular RNA (circRNA)
• competing endogenous RNA (ceRNA)
• long non-coding RNA (lncRNA)
• microRNA (miRNA)
• pseudogene

• 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

• Competing endogenous RNAs
• RNA-RNA crosstalk
• Shared MREs
• Sponge effect
• ceRNETs
• miRNAs

• Animals
• Gene Regulatory Networks
• Gene Silencing
• Humans
• MicroRNAs/genetics
• MicroRNAs/metabolism
• RNA, Messenger/chemistry
• RNA, Messenger/genetics
• RNA, Messenger/metabolism

Increasing evidence suggests a critical role for long noncoding RNAs (LncRNAs) and pseudogenes in cancer. Renal cell carcinoma (RCC), the most common primary renal neoplasm, is highly aggressive and difficult to treat because of its resistance to chemotherapy and radiotherapy. Despite many identified LncRNAs and pseudogenes, few have been clearly elucidated.

This study provides new insights into LncRNAs and pseudogenes in the prognosis of RCC. We searched an online database to interrogate alterations and clinical data on cBioPortal. We analysed LncRNA and pseudogene signatures to predict the prognosis of RCC based on a Cox model. We also found potential serum biomarkers of RCC and validated them in 32 RCC patients, as well as healthy controls.

Alterations were found in 2553 LncRNAs and 8901 pseudogenes and occurred in up to 23% of all cases. Among these, 27 LncRNAs and 45 pseudogenes were closely related to prognosis. We also identified signatures of LncRNAs and pseudogenes that can predict overall survival and recurrence of RCC. We then validated the relative levels of these LncRNAs and pseudogenes in the serum of 32 patients. Six of these, including LINC00520, PIK3CD-AS1, LINC01559, CEACAM22P, MSL3P1 and TREML3P, could be non-invasive biomarkers of RCC. Finally, we selected PIK3CD-AS1 to determine its role in RCC and found that upregulation of PIK3CD-AS1 was closely associated with higher tumour stage and metastasis.

These signatures of LncRNAs and pseudogenes can predict overall survival and recurrence of RCC. LINC00520, PIK3CD-AS1, LINC01559, CEACAM22P, MSL3P1 and TREML3P could be non-invasive biomarkers of RCC. These data suggest the important roles of LncRNAs and pseudogenes in RCC, and therefore provides us new insights into the prognosis of RCC.

The online version of this article (10.1186/s12935-018-0652-6) contains supplementary material, which is available to authorized users.

• Biomarker
• Long noncoding RNA
• Overall survival
• PIK3CD-AS1
• Pseudogenes
• Recurrence
• Renal cell carcinoma
• Signature
• cBioPortal

• DUXAP10
• ESCC
• EZH2
• p21
• proliferation

• LncRNA
• ceRNA
• gene regulation
• microRNA
• pseudogene

Noncoding RNAs (ncRNAs) constitute the majority of the human transcribed genome. This largest class of RNA transcripts plays diverse roles in a multitude of cellular processes, and has been implicated in many pathological conditions, especially cancer. The different subclasses of ncRNAs include microRNAs, a class of short ncRNAs; and a variety of long ncRNAs (lncRNAs), such as lincRNAs, antisense RNAs, pseudogenes, and circular RNAs. Many studies have demonstrated the involvement of these ncRNAs in competitive regulatory interactions, known as competing endogenous RNA (ceRNA) networks, whereby lncRNAs can act as microRNA decoys to modulate gene expression. These interactions are often interconnected, thus aberrant expression of any network component could derail the complex regulatory circuitry, culminating in cancer development and progression. Recent integrative analyses have provided evidence that new computational platforms and experimental approaches can be harnessed together to distinguish key ceRNA interactions in specific cancers, which could facilitate the identification of robust biomarkers and therapeutic targets, and hence, more effective cancer therapies and better patient outcome and survival.

• cancer
• ceRNA
• circRNA
• lncRNA
• miRNA
• pseudogene

Driven by genetic and epigenetic alterations, progression, therapy resistance and metastasis are frequent events in colorectal cancer (CRC). Although often speculated, the function of cell-cell contact for radiochemosensitivity, particularly associated with E-cadherin/catenin complex, warrants further clarification. In this study, we investigated the role of the E-cadherin/catenin complex proteins under more physiological three-dimensional (3D) cell culture conditions in a panel of CRC cell lines. In contrast to floating spheroids and growth in the laminin-rich matrix, collagen type 1 induced the formation of two distinct growth phenotypes, i.e., cell groups and single cells, in 5 out of the 8 CRC cell lines. Further characterization of these subpopulations revealed that, intriguingly, cell-cell contact proteins are important for invasion, but negligible for radiochemosensitivity, proliferation and adhesion. Despite the generation of genomic and transcriptomic data, we were unable to elucidate the mechanisms through which α-catenin affects collagen type 1 invasion. In a retrospective analysis of patients with rectal carcinoma, a low α-catenin expression trended with overall survival, as well as locoregional and distant control. Our results suggest that the E-cadherin/catenin complex proteins forming cell-cell contacts are mainly involved in the invasion, rather than the radiochemosensitivity of 3D grown CRC cells. Further studies are warranted in order to provide a better understanding of the molecular mechanisms controlling cell-cell adhesion in the context of radiochemoresistance.

Long non-coding RNAs (lncRNAs) have emerged as major players in many biological and pathological processes; however, investigation into the function of lncRNAs in the development and progression of cancer is in its infancy. Therefore, clarification of the mechanism by which cancer-related lncRNAs function is of critical importance in research on tumorigenesis. It has been demonstrated that the lncRNA XLOC_010588 is expressed at a low level in cervical cancer, and that this has significant impact on the proliferation of cervical cancer cells. However, the expression pattern and functional roles of XLOC_010588 in colorectal cancer (CRC) remain unclear. In the present study, it was demonstrated that the expression of XLOC_010588 was significantly higher in CRC tissues when compared with that in adjacent normal tissues, and that XLOC_010588 was closely associated with metastasis and poor prognosis, thus indicating that XLOC_010588 may function as an oncogene. Additionally, downregulation of XLOC_010588 expression markedly inhibited the invasion and migration of CRC cells. Furthermore, it was demonstrated that XLOC_010588 may regulate the progression of CRC via the epithelial-mesenchymal transition (EMT) pathway. Notably, downregulation of XLOC_010588 inhibited the invasion and migration of CRC cells by regulating genes associated with EMT. Our findings revealed that XLOC_010588 may be considered as a novel potential diagnostic biomarker in CRC.

• Colorectal cancer
• RNA
• ceRNA
• lncRNA
• microRNA

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

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.

• Anti-miRNA oligonucleotide
• Circular RNA
• Competing endogenous RNA
• Gene therapy
• Nanoparticle
• miRNA sponge