Regulation of autophagy

We further investigated the molecular mechanisms whereby Malat1 functioned on glioma cell autophagy and proliferation. We found that Malat1 served as an endogenous sponge to reduce miR-101 expression by directly binding to miR-101. Moreover, Malat1 abolished the suppression effects of miR-101 on glioma cell autophagy and proliferation, which involved in upregulating the expression of miR-101 targets STMN1, RAB5A and ATG4D.

Malat1 activates autophagy and promotes cell proliferation by sponging miR-101 and upregulating STMN1, RAB5A and ATG4D expression in glioma.

Regulation of autophagy

In conclusion, PVT1 overexpression increased the expression of Atg7 and Beclin1 by targeting miR-186, which induced protective autophagy, thus promoting glioma vascular endothelial cell proliferation, migration, and angiogenesis.

PVT1 affects growth of glioma microvascular endothelial cells by negatively regulating miR-186

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

Furthermore, we verified that c-Met was a directly target of miR-449b-5p. Rescue assays demonstrated NEAT1 functions a molecular sponge for miR-449b-5p and leads to the upregulation of c-Met.

Long noncoding RNA NEAT1 promotes glioma pathogenesis by regulating miR-449b-5p/c-Met axis

Regulation of autophagy

In conclusion, PVT1 overexpression increased the expression of Atg7 and Beclin1 by targeting miR-186, which induced protective autophagy, thus promoting glioma vascular endothelial cell proliferation, migration, and angiogenesis.

PVT1 affects growth of glioma microvascular endothelial cells by negatively regulating miR-186

Cell cycle； Oocyte meiosis；p53 signaling pathway；PI3K-Akt signaling pathway；Hepatitis B；Measles；Pathways in cancer；Viral carcinogenesis；Prostate cancer；Small cell lung cancer

Knockdown of KCNQ1OT1 decreased the expression level of Cyclin E2 (CCNE2) by binding to miR-370. Further, miR-370 bound to CCNE2 3'UTR region and decreased the expression of CCNE2. These results provided a comprehensive analysis of KCNQ1OT1-miR-370-CCNE2 axis in human glioma cells and might provide a novel strategy for glioma treatment.

Knockdown of Long Non-Coding RNA KCNQ1OT1 Restrained Glioma Cells' Malignancy by Activating miR-370/CCNE2 Axis

Ubiquitin mediated proteolysis

Further, MALAT1 suppresses cell viability by down-regulating miR-155. FBXW7 mRNA was identified as a direct target of miR-155 in glioma. The miR-155-induced tumorigenesis is mediated through FBXW7 function. Finally, we found that MALAT1 positively regulated FBXW7 expression, which was responsible for glioma progression mediated by MALAT1-miR-155 pathway.

Tumor-suppressive function of long noncoding RNA MALAT1 in glioma cells by suppressing miR-155 expression and activating FBXW7 function

The analysis of the mechanism of action revealed that the reduction of XIST inhibited the expression of the transcription factor forkhead box C1 (FOXC1) and zonula occludens 2 (ZO-2) by upregulating miR-137.

Knockdown of long non-coding RNA XIST increases blood-tumor barrier permeability and inhibits glioma angiogenesis by targeting miR-137

Maturity onset diabetes of the young

We also found that circ-TTBK2, but not linear TTBK2, acted as miR-217 sponge in a sequence-specific manner. In addition, upregulated circ-TTBK2 decreased miR-217 expression and there was a reciprocal negative feedback between them in an Argonaute2-dependent manner. Moreover, reintroduction of miR-217 significantly reversed circ-TTBK2-mediated promotion of glioma progression. HNF1β was a direct target of miR-217, and played oncogenic role in glioma cells.

TTBK2 circular RNA promotes glioma malignancy by regulating miR-217/HNF1β/Derlin-1 pathway

In addition, miR-140 dependent inhibitor of apoptosis-stimulating protein of p53 (iASPP) regulation was required in H19 induced glioma cell growth.

The lncRNA H19 interacts with miR-140 to modulate glioma growth by targeting iASPP

Taken together, UCA1 might promote proliferation and migration of glioma, to regulate the tumor growth and metastasis via miR-182 dependent iASPP regulation.

The lncRNA UCA1 interacts with miR-182 to modulate glioma proliferation and migration by targeting iASPP

Hepatitis B；Chemokine signaling pathway；HIF-1 signaling pathway；Jak-STAT signaling pathway；Adipocytokine signaling pathway； Toxoplasmosis；Proteoglycans in cancer；Hepatitis C； Measles；Epstein-Barr virus infection；Pathways in cancer；Acute myeloid leukemia；Pancreatic cancer；Viral carcinogenesis

At the molecular level, treatment by CRNDE knockdown or miR-384 overexpression resulted in a decrease of piwi-like RNA-mediated gene silencing 4 (PIWIL4) protein.

CRNDE Promotes Malignant Progression of Glioma by Attenuating miR-384/PIWIL4/STAT3 Axis

p53 signaling pathway；Inositol phosphate metabolism；Prostate cancer；Phosphatidylinositol signaling system；mTOR signaling pathway；PI3K-Akt signaling pathway；Focal adhesion；Tight junction；Hepatitis B；Pathways in cancer；Melanoma；Endometrial cancer；Glioma；Small cell lung cancer

CASC2 up-regulated PTEN protein and down-regulated p-AKT protein through regulating miR-181a, and the effect of CASC2 on PTEN and p-AKT could be partially restored by miR-181a. With TMZ-resistant glioma tissues, miR-181a was up-regulated while PTEN was down-regulated.

LncRNA CASC2 Interacts With miR-181a to Modulate Glioma Growth and Resistance to TMZ Through PTEN Pathway

p53 signaling pathway；Inositol phosphate metabolism；Prostate cancer；Phosphatidylinositol signaling system；mTOR signaling pathway；PI3K-Akt signaling pathway；Focal adhesion；Tight junction；Hepatitis B；Pathways in cancer；Melanoma；Endometrial cancer；Glioma；Small cell lung cancer

As expected, luciferase results verified the putative target site and also revealed the complementary binding between miR-19a and MEG3. miR-19a represses the expression of PTEN and promotes glioma cell proliferation, migration, and invasion

Long Noncoding RNA MEG3 Suppresses Glioma Cell Proliferation, Migration, and Invasion By Acting As Competing Endogenous RNA of MiR-19a

Endocytosis；Phagosome；Vasopressin-regulated water reabsorption；Amyotrophic lateral sclerosis (ALS)；Amoebiasis；Tuberculosis

We further investigated the molecular mechanisms whereby Malat1 functioned on glioma cell autophagy and proliferation. We found that Malat1 served as an endogenous sponge to reduce miR-101 expression by directly binding to miR-101. Moreover, Malat1 abolished the suppression effects of miR-101 on glioma cell autophagy and proliferation, which involved in upregulating the expression of miR-101 targets STMN1, RAB5A and ATG4D.

Malat1 activates autophagy and promotes cell proliferation by sponging miR-101 and upregulating STMN1, RAB5A and ATG4D expression in glioma.

Mechanistic investigations revealed that HOTAIR might act as an endogenous 'sponge' of miR-141, thereby regulating the derepression of SKA2.

Epigenetic modification of miR-141 regulates SKA2 by an endogenous 'sponge' HOTAIR in glioma

MAPK signaling pathway

We further investigated the molecular mechanisms whereby Malat1 functioned on glioma cell autophagy and proliferation. We found that Malat1 served as an endogenous sponge to reduce miR-101 expression by directly binding to miR-101. Moreover, Malat1 abolished the suppression effects of miR-101 on glioma cell autophagy and proliferation, which involved in upregulating the expression of miR-101 targets STMN1, RAB5A and ATG4D.

Malat1 activates autophagy and promotes cell proliferation by sponging miR-101 and upregulating STMN1, RAB5A and ATG4D expression in glioma.

In particular, ATB may act as a ceRNA, effectively becoming a sink for miR-200a, thereby modulating the derepression of TGF-β2.

Long non-coding RNA ATB promotes glioma malignancy by negatively regulating miR-200a

Inhibition of ECONEXIN upregulated miR-411-5p together with the downregulation of its target, Topoisomerase 2 alpha (TOP2A), in glioma cell lines, resulting in decreased cell proliferation. Our data demonstrated that ECONEXIN is a potential oncogene that regulates TOP2A by sponging miR-411-5p in glioma.

Oncogenic effects of evolutionarily conserved noncoding RNA ECONEXIN on gliomagenesis

Knockdown of H19 also decreased the VASH2 expression by up-regulating miR-29a.

Long non-coding RNA H19 regulates glioma angiogenesis and the biological behavior of glioma-associated endothelial cells by inhibiting microRNA-29a

Knockdown of H19 also decreased the VASH2 expression by up-regulating miR-29a.

Long non-coding RNA H19 regulates glioma angiogenesis and the biological behavior of glioma-associated endothelial cells by inhibiting microRNA-29a

Tight junction；Vibrio cholerae infection

The analysis of the mechanism of action revealed that the reduction of XIST inhibited the expression of the transcription factor forkhead box C1 (FOXC1) and zonula occludens 2 (ZO-2) by upregulating miR-137.

Knockdown of long non-coding RNA XIST increases blood-tumor barrier permeability and inhibits glioma angiogenesis by targeting miR-137