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

Moreover, silencing PVT1 by siRNA inhibited BCL2, CCND1, and FASN protein expression via miR-195 in osteosarcoma cells, and BCL2 inhibited the si-PVT1#1-induced apoptosis of U2OS cells.

Long non-coding RNA PVT1 promotes osteosarcoma development by acting as a molecular sponge to regulate miR-195

Protein processing in endoplasmic reticulum；Phagosome；Antigen processing and presentation；HTLV-I infection

Hsa_circ_0001564, located at 5q35.3 and its associated-gene symbol is CANX, was one of the significantly overexpressed circRNAs in osteosarcoma tissue, as well as in osteosarcoma cell lines. In functional experiments, hsa_circ_001564 knockdown significantly suppressed the proliferation activity, induced cell cycle arrest in G0/G1 phase, and promoted apoptosis in HOS and MG-63 cells. Subsequently, we explored the probable mechanism of hsa_circ_001564, and fortunately, bioinformatics analysis revealed that miR-29c-3p contained the complementary binding region with hsa_circ_0001564, which was confirmed by dual-luciferase reporter assa

Circular RNA hsa_circ_0001564 regulates osteosarcoma proliferation and apoptosis by acting miRNA sponge.

Cell cycle；p53 signaling pathway；Endometrial cancer；Melanoma；Thyroid cancer；PI3K-Akt signaling pathway；Pancreatic cancer；Wnt signaling pathway；Hippo signaling pathway；Prostate cancer；Acute myeloid leukemia；Focal adhesion；Viral myocarditis；Viral carcinogenesis；Colorectal cancer；Jak-STAT signaling pathway；Hepatitis B；Measles；Proteoglycans in cancer；Bladder cancer；Non-small cell lung cancer；HTLV-I infection；Small cell lung cancer；Pathways in cancer；Glioma；Chronic myeloid leukemia

Moreover, silencing PVT1 by siRNA inhibited BCL2, CCND1, and FASN protein expression via miR-195 in osteosarcoma cells, and BCL2 inhibited the si-PVT1#1-induced apoptosis of U2OS cells.

Long non-coding RNA PVT1 promotes osteosarcoma development by acting as a molecular sponge to regulate miR-195

Fatty acid biosynthesis；Metabolic pathways； Insulin signaling pathway

Moreover, silencing PVT1 by siRNA inhibited BCL2, CCND1, and FASN protein expression via miR-195 in osteosarcoma cells, and BCL2 inhibited the si-PVT1#1-induced apoptosis of U2OS cells.

Long non-coding RNA PVT1 promotes osteosarcoma development by acting as a molecular sponge to regulate miR-195

Starch and sucrose metabolism；Glycolysis / Gluconeogenesis；Fructose and mannose metabolism；Galactose metabolism；Amino sugar and nucleotide sugar metabolism；Butirosin and neomycin biosynthesis；Metabolic pathways；HIF-1 signaling pathway；Insulin signaling pathway；Type II diabetes mellitus ；Carbohydrate digestion and absorption

Functionally, knockdown of PVT1 exerted tumor-suppressive effect by suppressing cell proliferation, cell cycle progression, and invasion in vitro, whereas miR-497 inhibitor partially abolished the inhibition effect of si-PVT1. Overexpression of HK2 attenuated the miR-497 induced inhibition of cell growth and motility. Taken together, these findings suggested that PVT1 contributes to OS cell glucose metabolism, cell proliferation, and motility through the miR-497/HK2 pathway, and revealed a novel relation between lncRNA and the alteration of glycolysis in OS cells.

Long non-coding RNA PVT1 promotes glycolysis and tumor progression by regulating miR-497/HK2 axis in osteosarcoma.

Base excision repair

Moreover, knockdown of MALAT1 decreased HMGB1 expression, inhibited OS cell growth and promoted apoptosis, while miR-142-3p and miR-129-5p inhibitor partly restored the inhibitory effect of MALAT1 knockdown on HMGB1 expression, OS cell growth and the promotion of apoptosis.

MALAT1 promotes osteosarcoma development by regulation of HMGB1 via miR-142-3p and miR-129-5p

Base excision repair

Moreover, knockdown of MALAT1 decreased HMGB1 expression, inhibited OS cell growth and promoted apoptosis, while miR-142-3p and miR-129-5p inhibitor partly restored the inhibitory effect of MALAT1 knockdown on HMGB1 expression, OS cell growth and the promotion of apoptosis.

MALAT1 promotes osteosarcoma development by regulation of HMGB1 via miR-142-3p and miR-129-5p

Elevated LINC00161 increased cisplatin-induced apoptosis and reversed the cisplatin-resistant phenotype of osteosarcoma cells by upregulating IFIT2. Further mechanistic studies revealed that LINC00161 could sponge endogenous miR-645 and inhibit its activity leading to IFIT2 increase. In addition, we identified that LINC00161 enhanced cisplatin-induced apoptosis through regulation of the miR-645-IFIT2 pathway.

Long non-coding RNA LINC00161 sensitises osteosarcoma cells to cisplatin-induced apoptosis by regulating the miR-645-IFIT2 axis

Cytokine-cytokine receptor interaction；HIF-1 signaling pathway；PI3K-Akt signaling pathway；Jak-STAT signaling pathway；Hematopoietic cell lineage

Direct interaction of circ_0009910 and miR-449a was confirmed through dual-luciferase assays. Moreover, IL6R was predicted as a potential target of miR-449a. Overexpression of miR-449a decreased the mRNA and protein levels of IL6R.

Hsa_circ_0009910 promotes carcinogenesis by promoting the expression of miR-449a target IL6R in osteosarcoma

Proteoglycans in cancer

Finally, we affirmed that XIST regulated PDCD4 expression by competitively binding to miR-21-5p. XIST inhibited cell proliferation and cell mobility by competitively binding to miR-21-5p and upregulating PDCD4 in OS.

Long non-coding RNA XIST regulates PDCD4 expression by interacting with miR-21-5p and inhibits osteosarcoma cell growth and metastasis.

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

Furthermore, XIST could directly bind to miR-320b and repressed miR-320b expression. Moreover, XIST overexpression significantly relieved the inhibition on OS cell proliferation and invasion mediated by miR-320b overexpression, which involved the derepression Ras-relate protein RAP2B.

Long Non-Coding RNA XIST Promotes Osteosarcoma Progression by Targeting Ras-Related Protein RAP2B via miR-320b

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

Furthermore, we showed that H19 promotes metastasis through upregulation of ZEB1 and ZEB2 by competitively binding the miR-200 family.

H19 Functions as a ceRNA in Promoting Metastasis Through Decreasing miR-200s Activity in Osteosarcoma

Transcriptional misregulation in cancer

Furthermore, we showed that H19 promotes metastasis through upregulation of ZEB1 and ZEB2 by competitively binding the miR-200 family.

H19 Functions as a ceRNA in Promoting Metastasis Through Decreasing miR-200s Activity in Osteosarcoma

Transcriptional misregulation in cancer

Furthermore, we showed that H19 promotes metastasis through upregulation of ZEB1 and ZEB2 by competitively binding the miR-200 family.

H19 Functions as a ceRNA in Promoting Metastasis Through Decreasing miR-200s Activity in Osteosarcoma

Transcriptional misregulation in cancer

Furthermore, we showed that H19 promotes metastasis through upregulation of ZEB1 and ZEB2 by competitively binding the miR-200 family.

H19 Functions as a ceRNA in Promoting Metastasis Through Decreasing miR-200s Activity in Osteosarcoma

Transcriptional misregulation in cancer

Our results showed that ZEB1-AS1 functions as a molecular sponge for miR-200s and relieves the inhibition of ZEB1 caused by miR-200s.

Interplay between Long Noncoding RNA ZEB1-AS1 and miR-200s Regulates Osteosarcoma Cell Proliferation and Migration

Furthermore, we showed that H19 promotes metastasis through upregulation of ZEB1 and ZEB2 by competitively binding the miR-200 family.

H19 Functions as a ceRNA in Promoting Metastasis Through Decreasing miR-200s Activity in Osteosarcoma

Furthermore, we showed that H19 promotes metastasis through upregulation of ZEB1 and ZEB2 by competitively binding the miR-200 family.

H19 Functions as a ceRNA in Promoting Metastasis Through Decreasing miR-200s Activity in Osteosarcoma

Furthermore, we showed that H19 promotes metastasis through upregulation of ZEB1 and ZEB2 by competitively binding the miR-200 family.

H19 Functions as a ceRNA in Promoting Metastasis Through Decreasing miR-200s Activity in Osteosarcoma

Furthermore, we showed that H19 promotes metastasis through upregulation of ZEB1 and ZEB2 by competitively binding the miR-200 family.

H19 Functions as a ceRNA in Promoting Metastasis Through Decreasing miR-200s Activity in Osteosarcoma