PI3K-Akt signaling pathway

Knockdown of TUG1 decreased the ratio of apoptotic cells and promoted cells survival in vitro, which may be regulated by the elevated miRNA-9 expression and decreased Bcl2l11 protein.

LncRNA TUG1 sponges microRNA-9 to promote neurons apoptosis by up-regulated Bcl2l11 under ischemia

PI3K-Akt signaling pathway

Furthermore, TUG1 could directly interact with miR-9 and down-regulating miR-9 could efficiently reverse the function of TUG1 on the Bcl2l11 expression.

LncRNA TUG1 sponges microRNA-9 to promote neurons apoptosis by up-regulated Bcl2l11 under ischemia

HIF-1 signaling pathway；NF-kappa B signaling pathway；Protein processing in endoplasmic reticulum；Pathways in cancer；Small cell lung cancer；Prostate cancer；PI3K-Akt signaling pathway；Apoptosis；Focal adhesion； Neurotrophin signaling pathway；Cholinergic synapse；Amyotrophic lateral sclerosis (ALS)；Colorectal cancer；Hepatitis B；Epstein-Barr virus infection； Toxoplasmosis；Tuberculosis

The results of qRT-PCR and western-blot proved that the expression of microRNA-144 was significantly boosted and the expression level of c-Met mRNA and protein was inhibited after lncRNA-TUG1 was silenced

Inhibition of long non-coding RNA TUG1 on gastric cancer cell transference and invasion through regulating and controlling the expression of miR-144/c-Met axis

Furthermore, bioinformatics analysis showed that miR-186 could directly bind to TUG1, suggesting TUG1 might worked as a ceRNA to sponge miR-186. Extensively, our study also showed that CPEB2 was the direct target of miR-186 in colorectal cancer cells. Taken together, our study suggests that lncRNA TUG1 mediates MTX resistance in colorectal cancer via miR-186/CPEB2 axis.

TUG1 mediates methotrexate resistance in colorectal cancer via miR-186/CPEB2 axis

Furthermore, bioinformatics analysis showed that miR-186 could directly bind to TUG1, suggesting TUG1 might worked as a ceRNA to sponge miR-186. Extensively, our study also showed that CPEB2 was the direct target of miR-186 in colorectal cancer cells. Taken together, our study suggests that lncRNA TUG1 mediates MTX resistance in colorectal cancer via miR-186/CPEB2 axis.

TUG1 mediates methotrexate resistance in colorectal cancer via miR-186/CPEB2 axis.

Further experiments revealed that overexpressed TUG1 promoted cell proliferation, migration and contributed to EMT formation, whereas silenced TUG1 led to opposing results. Additionally, luciferase reporter assays, an RIP assay and an RNA-pulldown assay demonstrated that TUG1 could competitively sponge miR-382 and thereby regulate EZH2.

The Lncrna-TUG1/EZH2 Axis Promotes Pancreatic Cancer Cell Proliferation, Migration and EMT Phenotype Formation Through Sponging Mir-382.

Furthermore, Knockdown of TUG1 also down-regulated Heat shock transcription factor 2 (HSF2), a transcription factor of the heat shock transcription factor family, which was defined as a direct and functional downstream target of miR-144.

The long noncoding RNA TUG1 regulates blood-tumor barrier permeability by targeting miR-144

One carbon pool by folate；Metabolic pathways

TUG1 knockdown reduced proliferation, suppressed cell cycle progression, and promoted apoptosis of MCF-7 cells. The dual luciferase reporter assay showed that TUG1 could negatively regulate the expression of miR-9. MiR-9 inhibition abrogated the effect of TUG1 knockdown on the proliferation, cell cycle progression, and apoptosis of MCF-7 cells. TUG1 positively regulated the expression of MTHFD2 in breast cancer cells.

LncRNA Taurine-Upregulated Gene 1 Promotes Cell Proliferation by Inhibiting MicroRNA-9 in MCF-7 Cells

Moreover, TUG1 overturned the effect of miR-9-5p on the proliferation, colony formation, cell cycle arrest, and apoptosis in osteosarcoma cells, which involved the derepression of POU class 2 homeobox 1 (POU2F1) expression.

Long non-coding RNA TUG1 contributes to tumorigenesis of human osteosarcoma by sponging miR-9-5p and regulating POU2F1 expression

LncRNA TUG1 acts as an endogenous sponge of miR-377 and downregulates miR-377 expression levels, and thereby relieving the inhibition of its target gene PPARγ and alleviates extracellular matrix accumulation of mesangial cells, which provides a novel insight of diabetic nephropathy pathogenesis.

Long noncoding RNA TUG1 alleviates extracellular matrix accumulation via mediating microRNA-377 targeting of PPARγ in diabetic nephropathy

Vascular smooth muscle contraction；Chemokine signaling pathway；Proteoglycans in cancer； Wnt signaling pathway；TGF-beta signaling pathway；Axon guidance；Focal adhesion；Leukocyte transendothelial migration；Regulation of actin cytoskeleton；Pathogenic Escherichia coli infection；Shigellosis；Salmonella infection

The subsequent luciferase assay verified TUG1 was a target of miR-335-5p. Furthermore, the results of a real-time quantitative PCR showed that TUG1 and miR-335-5p could affect each other's expression. respectively. Finally, we affirmed that TUG1 affected ROCK1 expression and ROCK1-mediated migration/invasion by working as a competitive endogenous RNA (ceRNA) via miR-335-5p.

Long non-coding RNA TUG1 promotes migration and invasion by acting as a ceRNA of miR-335-5p in osteosarcoma cells

Transcriptional misregulation in cancer

Importantly, TUG1 directly interacted with miR-204-5p and downregulation of miR-204-5p efficiently reversed the suppression of Runx2 induced by TUG1 short hairpin RNA (shRNA).

LncRNA TUG1 sponges miR-204-5p to promote osteoblast differentiation through upregulating Runx2 in aortic valve calcification.

Hippo signaling pathway；MAPK signaling pathway；Cytokine-cytokine receptor interaction；Cell cycle；Endocytosis；TGF-beta signaling pathway；Renal cell carcinoma；Hypertrophic cardiomyopathy (HCM)；Chronic myeloid leukemia；Toxoplasmosis；Pathways in cancer；Osteoclast differentiation；HTLV-I infection；Proteoglycans in cancer；Intestinal immune network for IgA production；Rheumatoid arthritis；Dilated cardiomyopathy；Hepatitis B；Pancreatic cancer；Leishmaniasis；Tuberculosis；Chagas disease (American trypanosomiasis)；Colorectal cancer； Malaria

Mechanically, we found that TUG1 is upregulated by TGF-β1, and knockdown of TUG1 inhibited GBC cell EMT. Furthermore, we identified that miR-300, which has been reported as a suppressor in other types of cancer, is negatively regulated by TUG1.

Long non-coding RNA TUG1 promotes cell proliferation and metastasis by negatively regulating miR-300 in gallbladder carcinoma

HIF-1 signaling pathway；Cytokine-cytokine receptor interaction；mTOR signaling pathway；PI3K-Akt signaling pathway； VEGF signaling pathway；Focal adhesion； Pathways in cancer；Proteoglycans in cancer；Renal cell carcinoma；Pancreatic cancer；Bladder cancer；Rheumatoid arthritis

Moreover, knockdown of TUG1 reduced the expression of vascular endothelial growth factor A (VEGFA), which was defined as a functional downstream target of miR-299.

Long non-coding RNA taurine upregulated 1 enhances tumor-induced angiogenesis through inhibiting microRNA-299 in human glioblastoma

HIF-1 signaling pathway；Cytokine-cytokine receptor interaction；mTOR signaling pathway；PI3K-Akt signaling pathway； VEGF signaling pathway；Focal adhesion； Pathways in cancer；Proteoglycans in cancer；Renal cell carcinoma；Pancreatic cancer；Bladder cancer；Rheumatoid arthritis

TUG1 knockdown inhibits tumor growth and angiogenesis in vivo, and decreases hepatoblastoma cell viability, proliferation, migration, and invasion in vitro. TUG1, miR-34a-5p, and VEGFA constitutes to a regulatory network, and participates in regulating hepatoblastoma cell function, tumor progression, and tumor angiogenesis.

Targeting long non-coding RNA-TUG1 inhibits tumor growth and angiogenesis in hepatoblastoma