Long non-coding RNA TUG1 as a potential prognostic biomarker in human cancers: a meta-analysis

Liao

et al. 2019

Front. Mol. Neurosci.

Microglia plays a critical role in neuroinflammation after ischemic stroke by releasing diverse inflammatory cytokines. Long non-coding RNA taurine up-regulated gene 1 (lncRNA TUG1) is widely expressed in adult brain and has been reported to participate in multiple biological processes associated with nervous system diseases. However, the role of TUG1 in microglial activation remains unidentified. BV-2 microglial cells were cultured in vitro and TUG1 siRNA was used to knock down its RNA level. Microglial cells were subjected to oxygen-glucose deprivation (OGD) for 4 h following TUG1 siRNA or scramble siRNA transient transfection. After 24 h reoxygenation, TUG1 level and microglial M1/M2 phenotype, as well as releasing inflammatory cytokines and their role to viability of SH-SY5Y neuroblastoma cells were determined by quantitative real-time PCR (qRT-PCR), ELISA, immunofluorescence and western blot. In addition, miR-145a-5p, a putative microRNA to bind with TUG1 by bioinformatics analysis, was simultaneously examined, then the interaction of TUG1 with miR-145a-5p and the potential involvement of NF-κB pathway were further evaluated by RNA-RNA pull-down assay and western blot. The cellular level of TUG1 was transiently up-regulated in microglial cells 24 h after OGD treatment, with an inverse correlation to downregulated miR-145a-5p. TUG1 knockdown drove microglial M1-like to M2-like phenotypic transformation with reduced production of pro-inflammatory cytokines (tumor necrosis factor-α, TNF-α; interleukin-6, IL-6) and incremental release of anti-inflammatory cytokine (interleukin-10, IL-10), as a result, promoted the survival of SH-SY5Y cells. Meanwhile, TUG1 knockdown prevented OGD-induced activation of NF-κB pathway as well, represented by decreased ratios of p-p65/p65 and p-IκBα/IκBα proteins. Furthermore, we found that TUG1 could physically bind to miR-145a-5p while miR-145a-5p inhibitor abolished the protective effects of TUG1 knockdown through activation of NF-κB pathway, suggesting a negative interaction between TUG1 and miR-145a-5p. Our study demonstrated that lncRNA TUG1, sponging miR-145a-5p with negative interaction, could regulate microglial polarization and production of inflammatory cytokines at a relatively early stage after OGD insult, where NF-κB pathway might be involved, possibly providing a promising therapeutic target against inflammatory injury.

Section: Discussionmentioning

confidence: 99%

Long Non-coding RNA TUG1 Sponges Mir-145a-5p to Regulate Microglial Polarization After Oxygen-Glucose Deprivation

Liao

et al. 2019

Front. Mol. Neurosci.

“…TUG1 is a 7.1 kb intergenic lncRNA located on chromosome 22q12 [78,79,80]. TUG1 was firstly discovered to play a crucial role in mouse retinal development [78,79,81].…”

Section: Lncrnas In Lung Cancer (Lc)mentioning

confidence: 99%

“…TUG1 is a 7.1 kb intergenic lncRNA located on chromosome 22q12 [78,79,80]. TUG1 was firstly discovered to play a crucial role in mouse retinal development [78,79,81]. After that, TUG1 was found to have an important role in other cancers such as LC, HCC, BC, OC, GC, CRC, esophageal squamous cell carcinoma (ESCC), osteosarcoma, glioma, and bladder cancer [78,82].…”

Section: Lncrnas In Lung Cancer (Lc)mentioning

confidence: 99%

“…TUG1 is upregulated in the majority of the above cancer tissues but downregulated in LSCC and LAD tissues [78,79,80,82,83,84], suggesting that it may have tissue-specific expression patterns and a role in different human tumors [41]. NSCLC patients with high expression of TUG1 have a better prognosis [78]. In support, lower expression of TUG1 is associated with larger tumor size, advanced tumor lymph node metastasis (TNM) stage, and poorer OS in NSCLC patients [80].…”

Section: Lncrnas In Lung Cancer (Lc)mentioning

confidence: 99%

See 1 more Smart Citation

Long Non-Coding RNA in the Pathogenesis of Cancers

Chi

et al. 2019

Cells

643

452

The incidence and mortality rate of cancer has been quickly increasing in the past decades. At present, cancer has become the leading cause of death worldwide. Most of the cancers cannot be effectively diagnosed at the early stage. Although there are multiple therapeutic treatments, including surgery, radiotherapy, chemotherapy, and targeted drugs, their effectiveness is still limited. The overall survival rate of malignant cancers is still low. It is necessary to further study the mechanisms for malignant cancers, and explore new biomarkers and targets that are more sensitive and effective for early diagnosis, treatment, and prognosis of cancers than traditional biomarkers and methods. Long non-coding RNAs (lncRNAs) are a class of RNA transcripts with a length greater than 200 nucleotides. Generally, lncRNAs are not capable of encoding proteins or peptides. LncRNAs exert diverse biological functions by regulating gene expressions and functions at transcriptional, translational, and post-translational levels. In the past decade, it has been demonstrated that the dysregulated lncRNA profile is widely involved in the pathogenesis of many diseases, including cancer, metabolic disorders, and cardiovascular diseases. In particular, lncRNAs have been revealed to play an important role in tumor growth and metastasis. Many lncRNAs have been shown to be potential biomarkers and targets for the diagnosis and treatment of cancers. This review aims to briefly discuss the latest findings regarding the roles and mechanisms of some important lncRNAs in the pathogenesis of certain malignant cancers, including lung, breast, liver, and colorectal cancers, as well as hematological malignancies and neuroblastoma.

“…Meanwhile, in some types of breast cancer, non-smallcell lung cancer, and glioma, TUG1 was expressed at a low level when compared with noncancerous tissues and acts as a tumor suppressor [8][9][10]. Meta-analyses have attempted to demonstrate the potential diagnostic or prognostic role of TUG1 in cancer, but the conclusions were not consistent [11][12][13][14][15][16][17][18]. In recent years, studies examining TUG1 expression have been conducted through high-throughput wholegenome sequencing or quantitative real-time polymerase chain reaction (qRT-PCR), and we carried out the current meta-analysis to evaluate the role of TUG1 in tumors by expanding the number of samples and tumor types.…”

Section: Introductionmentioning

confidence: 99%

LncRNA Taurine Upregulated Gene 1 as a Potential Biomarker in the Clinicopathology and Prognosis of Multiple Malignant Tumors: A Meta-Analysis

Huang

et al. 2021

Disease Markers

Background. The lncRNA taurine upregulated gene 1 (TUG1) is a recently identified potential biomarker in cancer. However, its prognostic role in various cancers is inconsistent among published data. We conducted this meta-analysis to comprehensively confirm the prognostic effect of TUG1 in malignant tumors. Methods. We systemically analyzed the prognostic-predictive capacity of TUG1 through amplifying sample sizes and cancer types. STATA 12.0 was applied for this meta-analysis. Results. A total of 57 eligible studies were included in our meta-analysis. The pooled results suggested that overexpression of TUG1 was significantly correlated with unfavorable overall survival (OS) ( HR = 1.70 , p < 0.001 ), shorter recurrence-free survival (RFS) ( HR = 2.40 , p ≤ 0.001 ), and shorter event-free survival (EFS) ( HR = 1.88 , p < 0.001 ) in patients with cancer. In the subgroup analysis by cancer type, elevated TUG1 expression was associated with poorer survival in patients with gastrointestinal cancer, urinary tumors, gynecological tumors, hematological tumors, and osteosarcoma. However, high expression of TUG1 in respiratory tumors indicated a better prognosis. There was no correlation between high TUG1 expression and OS in patients with head and neck neoplasms or melanoma. Additionally, overexpression of TUG1 was found to be correlated with low-grade tumor differentiation, advanced tumor stage, positive lymphatic metastasis, and positive distant metastasis. Conclusions. High TUG1 expression correlates with poor prognosis and advanced clinicopathological features, verifying the prognostic-predictive capacity of TUG1 in tumors, especially in gastrointestinal cancer, urinary tumors, gynecological tumors, hematological tumors, and osteosarcoma. Meanwhile, the prognostic role of TUG1 in respiratory tumor may be opposite to other tumors.