The term long non-coding RNA (lncRNA) refers to a group of RNAs with length more than 200 nucleotides, limited protein-coding potential, and having widespread biological functions, including regulation of transcriptional patterns and protein activity, formation of endogenous small interfering RNAs (siRNAs) and natural microRNA (miRNA) sponges. Intervertebral disc degeneration (IDD) and osteoarthritis (OA) are the most common chronic, prevalent and age-related degenerative musculoskeletal disorders. Numbers of lncRNAs are differentially expressed in human degenerative nucleus pulposus tissue and OA cartilage. Moreover, some lncRNAs have been shown to be involved in multiple pathological processes during OA, including extracellular matrix (ECM) degradation, inflammatory responses, apoptosis and angiogenesis. In this review, we summarize current knowledge concerning lncRNAs, from their biogenesis, classification and biological functions to molecular mechanisms and therapeutic potential in IDD and OA.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/cpr.12313

lncRNAs: novel players in intervertebral disc degeneration and osteoarthritis

Osteoarthritis (OA) is a chronic joint disease and hard to cure at present. Accumulating evidence suggests long noncoding RNA-HOTAIR (lncRNA-HOTAIR) plays important role in OA progression. However, the underlying molecular mechanism of HOTAIR in OA progression has not been well elucidated. In the present study, we identified that HOTAIR level was upregulated in OA cartilage tissues. High expression of HOTAIR was correlated with modified Mankin scale, extracellular matrix (ECM) degradation and chondrocytes apoptosis. The expression of miR-17-5p was down-regulated, while alpha-1, 2 fucosyltransferase 2 (FUT2) was increased in OA progression. Luciferase reporter and RNA immunoprecipitation (RIP) assays indicated that HOTAIR could directly bind to miR-17-5p and indirectly upregulate FUT2 level. Functional investigation revealed HOTAIR and FUT2 aggravated ECM degradation and chondrocytes apoptosis, and this effect could be reversed by miR-17-5p. Altered FUT2 modulated the activity of wnt/β-catenin pathway and HOTAIR/miR-17-5p also mediated wnt/β-catenin pathway through FUT2. Collectively, our findings indicated that HOTAIR/miR-17-5p/FUT2 axis contributed to OA progression via wnt/β-catenin pathway, which might provide novel insights into the function of lncRNA-driven in OA.

/pdf/long-non-coding-rna-hotair-promotes-osteoarthritis-wjj1c2f6b5.pdf

Long non-coding RNA HOTAIR promotes osteoarthritis progression via miR-17-5p/FUT2/β-catenin axis

We review the most well characterized long non-coding RNAs (lncRNAs) with important roles in hallmarks of cancer, additionally including lncRNAs with a higher potential for clinical application. LncRNAs are transcripts larger than 200 nucleotides in length that do not appear to have protein-coding potential, although some of those may produce small functional peptides. These transcripts have attracted significant attention from researchers as a result of their role in genetic regulation, including epigenetic, transcriptional and post-transcriptional regulation, being involved in numerous biological processes, as well as being associated with multifactorial diseases, including tumorigenesis. The hallmarks of cancer include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis and activating invasion/metastasis. Additionally, genome instability, inflammation, reprogramming of energy metabolism and evading immune destruction and lncRNAs are implicated in all hallmarks of cancer. Based on the great number of studies describing lncRNAs associated with diverse aspects of most tumor types, lncRNAs have essential roles in potentially all biological features of cancer cells and show great utility as diagnostic and prognostic markers, as exemplified by PCA3 lncRNA detection in prostate cancer diagnosis.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jgm.3065

Long non-coding RNAs in cancer: Another layer of complexity.

Osteoarthritis (OA) is a chronic joint disease and there is no a definitive cure at present. Long non-coding RNAs (lncRNAs) have been confirmed to play important roles in the development of OA. However, the underlying mechanism of lncRNA maternally expressed gene 3 (MEG3) in OA has not been well elucidated. The rat OA model and interleukin-1β (IL-1β)-induced rat chondrocytes were constructed. The expression pattern of lncRNA MEG3 and miR-16 was detected by RT-qPCR assay in cartilage tissues of rat OA model. The effect of MEG3 and miR-16 on IL-1β-induced chondrocytes was evaluated on the basis of cell viability and apoptosis. Then, the interaction among MEG3, miR-16 SMAD7 was explored by dual-luciferase reporter assay and RIP assay. It is found that lncRNA MEG3 was down-regulated and miR-16 was up-regulated in rat OA cartilage tissues. MEG3 knockdown promoted proliferation and inhibited apoptosis, while miR-16 knockdown suppressed proliferation and promoted apoptosis in IL-1β-induced rat chondrocytes. Moreover, MEG3 was involved in miR-16 pathway and MEG3 suppressed miR-16 expression. Additionally, SMAD7 was a target gene of miR-16 and miR-16 suppressed SMAD7 expression in IL-1β-induced chondrocytes. Moreover, the expression of SMAD7 induced by MEG3 or si-MEG3 was markedly reversed by the introduction of miR-16 or anti-miR-16. Furthermore, MEG3 exerted its anti-proliferation and pro-apoptosis by regulating miR-16 and SMAD7. MEG3 was down-regulated and miR-16 was up-regulated in cartilage tissues of rat OA model. MEG3 knockdown might lead to the progression of OA through miR-16/SMAD7 axis.

/pdf/the-lncrna-meg3-downregulation-leads-to-osteoarthritis-2cwh4iwl3n.pdf

The lncRNA MEG3 downregulation leads to osteoarthritis progression via miR-16/SMAD7 axis

The purpose of this study is to investigate the role of exosomal lncRNAs from plasma and from synovial fluid in patients with osteoarthritis (OA) and to determine their diagnostic value in distinguishing the early stage of OA from progressive stage of OA. Participants were divided into three groups. The control  group included 20 pre-arthritic patients, early OA group included 20 patients in the early OA, and late-stage OA group included 22 patients in the late-stage OA. For all subjects, blood sample from cubital vein and synovial fluid sample from knee joint were collected. Exosomes were extracted by ultracentrifugation. LncRNAs were extracted from exosomes using RNeasy kit, and the expression of several exosomal lncRNAs, including HOTAIR, PCGEM1, and GAS5, was measured using quantitative real-time polymerase chain reaction (qPCR). Also, Spearman’s correlation test was performed to determine the correlation between exosomal lncRNA PCGEM1 and WOMAC index. Last, the receiver operating characteristic (ROC) curve was performed to determine the diagnostic value of exosomal lncRNA PCGEM1 in distinguishing the different stages of OA. First, for plasma, both the expression of exosomes in three groups and the relative expression of exosomal lncRNAs chosen showed no significant difference among three groups, while for synovial fluid sample, the expression of exosomes in early OA and late-stage OA was much markedly higher than that in controls; and the expression of exosomal lncRNA PCGEM1 was markedly higher in late-stage OA than in early OA, and markedly higher in early OA than controls. Both the expression of exosomal lncRNA HOTAIR and GAS5 showed no significant difference among these groups. Second, there was a positive relationship between exosomal lncRNA PCGEM1 and WOMAC Index. Last, ROC curve showed that the area values under the curve of exosomal lncRNA PCGEM1 were 0.879, 0.757, and 0.593, respectively. Our study demonstrated that exosomal lncRNA PCGEM1 might be a powerful indicator in distinguishing the early OA from the late-stage OA.

Synovial fluid-derived exosomal lncRNA PCGEM1 as biomarker for the different stages of osteoarthritis

Upregulation of lncRNA HOTAIR contributes to IL-1β-induced MMP overexpression and chondrocytes apoptosis in temporomandibular joint osteoarthritis.

Retinoblastoma is the most frequently occurring tumour in the eyes in early childhood. Novel targets that are important for the diagnosis or treatment of retinoblastoma could be valuable in increasing the survival rate of patients affected by this disease. Long non-coding RNAs (lncRNAs) are a recently discovered type of RNAs with no proteincoding function; yet it has become increasingly clear that lncRNAs are responsible for important gene regulatory functions in various diseases. In this study, the expression of lncRNA HOTAIR was measured by qRT-PCR, and HOTAIR expression was found to be significantly upregulated in human retinoblastomas tissues as compared with that in paracancerous tissues. Knockdown of HOTAIR restricted the proliferation and invasion of the more invasive retinoblastoma Y79 cells, and led to G0/G1 arrest, possibly through inhibiting phospho-RB1, RB1 and CCNE. Furthermore, we found that the Notch signalling pathway was activated abnormally in retinoblastoma cell lines, while knockdown of HOTAIR attenuated the endogenous Notch signalling pathway in vitro and in vivo. In addition, knockdown of HOTAIR could inhibit the tumour progression in a xenograft model of retinoblastoma. In summary, our findings indicate that HOTAIR may play important roles in retinoblastoma progression via Notch pathway. HOTAIR has the potential to enhance the development of novel targeted diagnostic and therapeutic approaches for retinoblastoma.

Long non-coding RNA HOTAIR regulates proliferation and invasion via activating Notch signalling pathway in retinoblastoma.

Introduction To determine the clinical effects of laparoscopic surgery (LS) in the treatment of endometriosis and endometriosis-fertility. Methods Two hundred twenty-six patients with endometriosis who underwent LS (LS group, n = 176) or laparotomy (LT group, n = 50) at the Third Hospital of Shijiazhuang City from June 2011 to June 2013 were included in this study, and their clinical outcomes for endometriosis and infertility were compared. All patients were followed up for 1 year after surgery to determine postoperative pregnancies in patients with endometriosis. Results The operative times between the LS and LT groups were not significantly different (P > 0.05); however, the length of stay in the hospital and blood loss in the LS group were significantly different from the LT group (P < 0.05). The incidence of postoperative symptoms were lower in the LS group than the LT group (P < 0.05). The postoperative pregnancy rates in the two groups were significantly different, including the infertility patients (P < 0.05). Conclusions Compared with LT, LS significantly reduced pain and improved the quality of life in women with endometriosis. These results can provide a reference for the clinical treatment of endometriosis.

Clinical effects of laparoscopic surgery for the treatment of endometriosis and endometriosis-fertility: A retrospective study of 226 cases

Background Dementia have brought great challenges to patients, families and society. Numerous art therapies for patients with dementia have been developed in recent years. However, it is still unclear which art therapy represents the optimal strategy for promoting physical and mental health. Objectives To compare the efficacy of various art therapies in improving cognitive function, activity of daily living, depression, anxiety, agitation behavior and quality of life, and rank the art therapies for practice consideration. Methods A comprehensive literature search was performed in eight electronic databases from their inception to April 2022. Two authors independently completed study selection, data extraction, and assessed methodological quality according to the revised version of the Cochrane tool (RoB 2). Comparative evaluation of different art therapies’ effect was performed by conducting network meta-analysis. The study protocol was registered at PROSPERO. Results A total of 39 randomized controlled trials involving 2801 participants were included. Calligraphy therapy (MD = 4.39) and reminiscence therapy (MD = 2.53) significantly improved cognitive function compared with the usual care, and reminiscence therapy (MD = 1.75) significantly enhanced cognitive function compared with music therapy. Horticultural therapy significantly decreased agitation behavior compared with the usual care (MD = −31.34), music therapy (MD = −26.66), reading therapy (MD = −28.44) and reminiscence therapy (MD = −27.32). In addition, calligraphy therapy (MD = 9.00) improved quality of life compared with the usual care. Conclusion Calligraphy therapy might be the most effective art therapy for improving cognitive function and quality of life. Horticultural therapy might be the best art therapy for decreasing agitation behavior. Health-care professionals could consider applying these art therapies to improve cognitive function, agitation behavior and quality of life in patients with dementia.

/pdf/comparative-efficacy-of-various-art-therapies-for-patients-2svhqyg1.pdf

Lixia Tan

Papers

Upregulation of lncRNA HOTAIR contributes to IL-1β-induced MMP overexpression and chondrocytes apoptosis in temporomandibular joint osteoarthritis.

Long non-coding RNA HOTAIR regulates proliferation and invasion via activating Notch signalling pathway in retinoblastoma.

Clinical effects of laparoscopic surgery for the treatment of endometriosis and endometriosis-fertility: A retrospective study of 226 cases

Comparative efficacy of various art therapies for patients with dementia: A network meta-analysis of randomized controlled trials