State of the art technologies to explore long non‐coding RNAs in cancer

Long non‐coding RNAs (lncRNAs) comprise a vast repertoire of RNAs playing a wide variety of crucial roles in tissue physiology in a cell‐specific manner. Despite being engaged in myriads of regulatory mechanisms, many lncRNAs have still remained to be assigned any functions. A constellation of experimental techniques including single‐molecule RNA in situ hybridization (sm‐RNA FISH), cross‐linking and immunoprecipitation (CLIP), RNA interference (RNAi), Clustered regularly interspaced short palindromic repeats (CRISPR) and so forth has been employed to shed light on lncRNA cellular localization, structure, interaction networks and functions. Here, we review these and other experimental approaches in common use for identification and characterization of lncRNAs, particularly those involved in different types of cancer, with focus on merits and demerits of each technique.     

Genome‐wide characterization and developmental expression profiling of long non‐coding RNAs in Sogatella furcifera

The genome‐wide characterization of long non‐coding RNA (lncRNA) in insects demonstrates their importance in fundamental biological processes. Essentially, an in‐depth understanding of the functional repertoire of lncRNA in insects is pivotal to insect resources utilization and sustainable pest control. Using a custom bioinformatics pipeline, we identified 1861 lncRNAs encoded by 1852 loci in the Sogatella furcifera genome. We profiled lncRNA expression in different developmental stages and observed that the expression of lncRNAs is more highly temporally restricted compared to protein‐coding genes. More up‐regulated Sogatella furcifera lncRNA expressed in the embryo, 4th and 5th instars, suggesting that increased lncRNA levels may play a role in these developmental stages. We compared the relationship between the expression of Sogatella furcifera lncRNA and its nearest protein gene and found that lncRNAs were more correlated to their downstream coding neighbors on the opposite strand. Our genome‐wide profiling of lncRNAs in Sogatella furcifera identifies exciting candidates for characterization of lncRNAs, and also provides information on lncRNA regulation during insect development.     

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.     

Small regulatory non‐coding RNAs in bacteria: physiology and mechanistic aspects

Regulatory ncRNAs (non‐coding RNAs) adjust bacterial physiology in response to environmental cues. ncRNAs can base‐pair to mRNAs and change their translation efficiency and/or their stability, or they can bind to proteins and modulate their activity. ncRNAs have been discovered in several species throughout the bacterial kingdom. This review illustrates the diversity of physiological processes and molecular mechanisms where ncRNAs are key regulators.     

Emerging roles of non‐coding RNAs in scoliosis

Scoliosis, a complex three‐dimensional deformity of the spine with the Cobb angle (a measure of the spinal lateral curvature) >10 degree, encompasses a spectrum of pathologies, including congenital, idiopathic, syndromic and neuromuscular aetiologies. The pathogenesis is multifactorial involving both environmental and genetic factors but the exact cellular and molecular mechanisms of disease development remain largely unknown. Emerging evidence showed that non‐coding RNAs (ncRNAs), namely microRNAs, long ncRNAs and circular RNAs, are deregulated in many orthopaedic diseases, including scoliosis. Importantly, these deregulated ncRNAs functionally participate in the initiation and progression of scoliosis. Here, we review recent progress in ncRNA research on scoliosis.     

Overexpression of long non‐coding RNA ANRIL promotes post‐ischaemic angiogenesis and improves cardiac functions by targeting Akt

Angiogenesis is critical for re‐establishing the blood supply to the surviving myocardium after myocardial infarction (MI). Long non‐coding RNA ANRIL (lncRNA‐ANRIL) has been reported to regulate endothelial functions in cardiovascular diseases. This study was to determine the role of lncRNA‐ANRIL in Akt regulation and cardiac functions after MI. Human umbilical vein endothelial cells (HUVECs) were exposed to oxygen‐glucose deprivation (OGD) to mimic in vivo ischaemia. The MI model in mice was induced by ligating left anterior descending coronary artery. OGD remarkably decreased lncRNA‐ANRIL expression level, reduced the phosphorylated levels of Akt and eNOS proteins, and inhibited NO release and cell viability, which were duplicated by shRNA‐mediated gene knockdown of lncRNA‐ANRIL. Conversely, all these effects induced by OGD were abolished by adenovirus‐mediated overexpression of lncRNA‐ANRIL in HUVECs. Further, OGD impaired cell migrations and tube formations in HUVECs, which were reversed by lncRNA‐ANRIL overexpression or Akt up‐regulation. RNA immunoprecipitation analysis indicated that the affinity of lncRNA‐ANRIL to Akt protein was increased in OGD‐treated cells. In animal studies, adenovirus‐mediated lncRNA‐ANRIL overexpression increased the phosphorylated levels of Akt and eNOS, promoted post‐ischaemic angiogenesis and improved heart functions in mice with MI surgery. LncRNA‐ANRIL regulates Akt phosphorylation to improve endothelial functions, which promotes angiogenesis and improves cardiac functions in mice following MI. In this perspective, targeting lncRNA‐ANRIL/Akt may be considered to develop a drug to treat angiogenesis‐related diseases.     

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.     

Construction of competitive endogenous RNA network reveals regulatory role of long non‐coding RNAs in type 2 diabetes mellitus

Increasing epidemic of type 2 diabetes mellitus (T2DM) and its comorbidities makes it urgent to understand the pathogenesis and regulatory mechanism. However, little is known about the regulatory role of lncRNAs in diabetes. Here, we constructed a T2DM‐related competitive endogenous RNA (ceRNA) network (DMCN) to explore biological function of lncRNAs during the development of diabetes mellitus. This network contained 351 nodes including 98 mRNAs, 86 microRNAs and 167 lncRNAs. Functional analysis showed that the mRNAs in DMCN were annotated into some diabetes‐related pathways. Furthermore, mTOR‐centred subnetwork was extracted and ncRNA‐involved mTOR pathway was established. Finally, we validated that NEAT1 was potentially communicated with mTOR signalling target protein mLST8 via the association with miR‐181b. These findings provide significant insight into lncRNA regulatory network in T2DM.