Long non‐coding RNAs in melanoma

Melanoma is the most lethal cutaneous cancer with a highly aggressive and metastatic phenotype. While recent genetic and epigenetic studies have shed new insights into the mechanism of melanoma development, the involvement of regulatory non‐coding RNAs remain unclear. Long non‐coding RNAs (lncRNAs) are a group of endogenous non‐protein‐coding RNAs with the capacity to regulate gene expression at multiple levels. Recent evidences have shown that lncRNAs can regulate many cellular processes, such as cell proliferation, differentiation, migration and invasion. In the melanoma, deregulation of a number of lncRNAs, such as HOTAIR, MALAT1, BANCR, ANRIL, SPRY‐IT1 and SAMMSON, have been reported. Our review summarizes the functional role of lncRNAs in melanoma and their potential clinical application for diagnosis, prognostication and treatment.     

Temporal expression and functional analysis of long non‐coding RNAs in colorectal cancer initiation

Long non‐coding RNAs (lncRNAs) have potential applications in clinical diagnosis and targeted cancer therapies. However, the expression profile of lncRNAs in colorectal cancer (CRC) initiation is still unclear. In this study, the expression profiles of lncRNAs and mRNAs were determined by microarray at specific tumour stages in an AOM/DSS‐induced primary colon cancer model. The temporal expression of lncRNAs was analysed by K‐means clustering. Additionally, weighted correlation network analysis (WGCNA) and gene ontology analysis were performed to construct co‐expression networks and establish functions of the identified lncRNAs and mRNAs. Our results suggested that 4307 lncRNAs and 5798 mRNAs are deregulated during CRC initiation. These differential expression genes (DEGs) exhibited a clear correlation with the differential stage of tumour initiation. WGCNA results suggested that a series of hub lncRNAs are involved in regulating cell stemness, colon inflammation, oxidative stress response and cell death at each stage. Among them, lncRNA H19 was up‐regulated in colon tumours and correlated with poor patient prognosis. Collectively, we have been the first to demonstrate the temporal expression and function of lncRNAs in CRC initiation. These results provide novel diagnosis and therapy targets for CRC.     

Long non‐coding RNAs in non‐small cell lung cancer as biomarkers and therapeutic targets

Lung cancer‐associated mortality is the most common cause of cancer death worldwide. Non‐coding RNAs (ncRNAs), with no protein‐coding ability, have multiple biological roles. Long non‐coding RNAs (lncRNAs) are a recently characterized class of ncRNAs that are over 200 nucleotides in length. Many lncRNAs have the ability of facilitating or inhibiting the development and progression of tumours, including non‐small cell lung cancer (NSCLC). Because of their fundamental roles in regulating gene expression, along with their involvement in the biological mechanisms underlying tumourigenesis, they are a promising class of tissue‐ and/or blood‐based cancer biomarkers. In this review, we highlight the emerging roles of lncRNAs in NSCLC, and discuss their potential clinical applications as diagnostic and prognostic markers and as therapeutic targets.     

ZEB1‐AS1: A crucial cancer‐related long non‐coding RNA

Long non‐coding RNAs (lncRNAs) recently emerge as a novel class of non‐coding RNAs (ncRNAs) with larger than 200 nucleotides in length. Due to lack an obvious open reading frame, lncRNAs have no or limited protein‐coding potential. To date, accumulating evidence indicates the vital regulatory function of lncRNAs in pathological processes of human diseases, especially in carcinogenesis and development. Deregulation of lncRNAs not only alters cellular biological behavior, such as proliferation, migration and invasion, but also represents the poor clinical outcomes. Zinc finger E‐box binding homeobox 1 antisense 1 (ZEB1‐AS1), an outstanding cancer‐related lncRNA, is identified as an oncogenic regulator in diverse malignancies. Dysregulation of ZEB1‐AS1 has been demonstrated to exhibit a pivotal role in tumorigenesis and progression, suggesting its potential clinical value as a promising biomarker or therapeutic target for cancers. In this review, we make a summary on the current findings regarding the biological functions, underlying mechanisms and clinical significance of ZEB1‐AS1 in cancer progression.     

The latest progress on miR‐374 and its functional implications in physiological and pathological processes

Non‐coding RNAs (ncRNAs) have been emerging players in cell development, differentiation, proliferation and apoptosis. Based on their differences in length and structure, they are subdivided into several categories including long non‐coding RNAs (lncRNAs >200nt), stable non‐coding RNAs (60‐300nt), microRNAs (miRs or miRNAs, 18‐24nt), circular RNAs, piwi‐interacting RNAs (26‐31nt) and small interfering RNAs (about 21nt). Therein, miRNAs not only directly regulate gene expression through pairing of nucleotide bases between the miRNA sequence and a specific mRNA that leads to the translational repression or degradation of the target mRNA, but also indirectly affect the function of downstream genes through interactions with lncRNAs and circRNAs. The latest studies have highlighted their importance in physiological and pathological processes. MiR‐374 family member are located at the X‐chromosome inactivation center. In recent years, numerous researches have uncovered that miR‐374 family members play an indispensable regulatory role, such as in reproductive disorders, cell growth and differentiation, calcium handling in the kidney, various cancers and epilepsy. In this review, we mainly focus on the role of miR‐374 family members in multiple physiological and pathological processes. More specifically, we also summarize their promising potential as novel prognostic biomarkers and therapeutic targets from bench to bedside.     

LncRNA‐mRNA expression profiles and functional networks in osteoclast differentiation

Human osteoclasts are differentiated from CD14⁺ monocytes and are responsible for bone resorption. Long non‐coding RNAs (lncRNAs) have been proved to be significantly involved in multiple biologic processes, especially in cell differentiation. However, the effect of lncRNAs in osteoclast differentiation is less appreciated. In our study, RNA sequencing (RNA‐seq) was used to identify the expression profiles of lncRNAs and mRNAs in osteoclast differentiation. The results demonstrated that expressions of 1117 lncRNAs and 296 mRNAs were significantly altered after osteoclast differentiation. qRT‐PCR assays were performed to confirm the expression profiles, and the results were almost consistent with the RNA‐seq data. GO and KEGG analyses were used to predict the functions of these differentially expressed mRNA and lncRNAs. The Path‐net analysis demonstrated that MAPK pathway, PI3K‐AKT pathway and NF‐kappa B pathway played important roles in osteoclast differentiation. Co‐expression networks and competing endogenous RNA networks indicated that ENSG00000257764.2‐miR‐106a‐5p‐TIMP2 may play a central role in osteoclast differentiation. Our study provides a foundation to further understand the role and underlying mechanism of lncRNAs in osteoclast differentiation, in which many of them could be potential targets for bone metabolic disease.     

Long non‐coding RNA FEZF1‐AS1 promotes breast cancer stemness and tumorigenesis via targeting miR‐30a/Nanog axis

Long non‐coding RNAs (lncRNAs) have been verified to modulate the tumorigenesis of breast cancer at multiple levels. In present study, we aim to investigate the role of lncRNA FEZF1‐AS1 on breast cancer‐stem like cells (BCSC) and the potential regulatory mechanism. In breast cancer tissue, lncRNA FEZF1‐AS1 was up‐regulated compared with controls and indicated poor prognosis of breast cancer patients. In vitro experiments, FEZF1‐AS1 was significantly over‐expressed in breast cancer cells, especially in sphere subpopulation compared with parental subpopulation. Loss‐of‐functional indicated that, in BCSC cells (MDA‐MB‐231 CSC, MCF‐7 CSC), FEZF1‐AS1 knockdown reduced the CD44⁺/CD24^? rate, the mammosphere‐forming ability, stem factors (Nanog, Oct4, SOX2), and inhibited the proliferation, migration and invasion. In vivo, FEZF1‐AS1 knockdown inhibited the breast cancer cells growth. Bioinformatics analysis tools and series of validation experiments confirmed that FEZF1‐AS1 modulated BCSC and Nanog expression through sponging miR‐30a, suggesting the regulation of FEZF1‐AS1/miR‐30a/Nanog. In summary, our study validate the important role of FEZF1‐AS1/miR‐30a/Nanog in breast cancer stemness and tumorigenesis, providing a novel insight and treatment strategy for breast cancer.     

Aberrantly expressed long non‐coding RNAs in air pollution‐induced congenital defects

Air pollution has been a serious public health issue over the past few decades particularly in developing countries. Air pollution exposure during pregnancy poses potential threat to offspring as the deleterious substances might pass through placenta to alter foetal development. A growing number of studies have demonstrated that long non‐coding RNAs (lncRNAs) participate in the development of many diseases, including congenital defects. Here, we used RNA sequencing to identify differentially expressed lncRNAs in air pollution‐exposed rat embryos compared with control group. Our data suggested that 554 lncRNAs (216 up‐regulated and 338 down‐regulated) were significantly differentially expressed in the air pollution‐exposed embryos. Moreover, potential cellular functions of these deregulated lncRNAs were predicted via KEGG signal pathway/GO enrichment analyses, which suggested the possible involvements of neurological process, sensory perception of smell and the G‐protein signalling pathway. Furthermore, potential functional network of deregulated lncRNAs and their correlated mRNAs in the development of congenital spinal abnormality was established. Our data suggested that lncRNAs may play a vital role in the pathophysiology of air pollution‐exposed congenital spinal malformation.