Cholinergic synapse；HIF-1 signaling pathway；Chemokine signaling pathway；MAPK signaling pathway；Small cell lung cancer；Toll-like receptor signaling pathway；Fc epsilon RI signaling pathway；T cell receptor signaling pathway；ErbB signaling pathway；Carbohydrate digestion and absorption；Chagas disease (American trypanosomiasis)；mTOR signaling pathway；PI3K-Akt signaling pathway；Hepatitis B；HTLV-I infection；Pathways in cancer；Toxoplasmosis；Colorectal cancer；Endometrial cancer；Jak-STAT signaling pathway；Neurotrophin signaling pathway；Influenza A；Proteoglycans in cancer； Measles；Dopaminergic synapse；Tuberculosis；Prostate cancer；Non-small cell lung cancer；Apoptosis；Progesterone-mediated oocyte maturation；Melanoma；Chronic myeloid leukemia； B cell receptor signaling pathway； Insulin signaling pathway；Renal cell carcinoma；Estrogen signaling pathway；VEGF signaling pathway；Osteoclast differentiation；Glioma；Epstein-Barr virus infection； Focal adhesion；Tight junction；Hepatitis C；Fc gamma R-mediated phagocytosis；Pancreatic cancer；Acute myeloid leukemia；Adipocytokine signaling pathway

In particular, our results suggested that lncRNA-XIST may act as a competitive endogenous RNA, effectively becoming a sink for miR-494, leading to derepression of its target gene, phosphatase and tensin homolog deleted on chromosome ten (PTEN). In addition, an inverse relationship between lncRNA-XIST and miR-494 was observed in spinal cord tissues of SCI rats. Further study demonstrated that antagomiR-494 could reverse the protective effects of lncRNA-XIST knockdown on SCI rats through blocking the PTEN/PI3K/AKT signaling pathway.

Long Coding RNA XIST Contributes to Neuronal Apoptosis through the Downregulation of AKT Phosphorylation and Is Negatively Regulated by miR-494 in Rat Spinal Cord Injury

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

We further identified reciprocal repression between XIST and miR-449a, which eventually influenced the expression of Bcl-2: XIST functioned as a miRNA sponge of miR-449a, which was a negative regulator of Bcl-2.

The lncRNA XIST exhibits oncogenic properties via regulation of miR-449a and Bcl-2 in human non-small cell lung cancerThis article has been corrected since Advanced Online Publication, and an erratum is also printed in this issue

Glioma；Cell cycle；Hepatitis B；HTLV-I infection；Pathways in cancer；Pancreatic cancer；Prostate cancer；Melanoma；Bladder cancer；Non-small cell lung cancer； Chronic myeloid leukemia；Small cell lung cancer

Additionally, mechanistic analysis revealed that XIST up-regulated the expression of miR-34a-5p targeted gene E2F3 through acting as a competitive 'sponge' of miR-34a-5p.

Long non-coding RNA XIST exerts oncogenic functions in human nasopharyngeal carcinoma by targeting miR-34a-5p

HIF-1 signaling pathway； MAPK signaling pathway； Endometrial cancer；Glioma；ErbB signaling pathway；Calcium signaling pathway；Cytokine-cytokine receptor interaction；Proteoglycans in cancer；Prostate cancer；Endocytosis；GnRH signaling pathway；PI3K-Akt signaling pathway；Dorso-ventral axis formation；Non-small cell lung cancer；Pancreatic cancer；Melanoma；Bladder cancer；Focal adhesion；Hepatitis C；Adherens junction；Gap junction；Epithelial cell signaling in Helicobacter pylori infection；Regulation of actin cytoskeleton；Pathways in cancer；Estrogen signaling pathway

Moreover, as exhibited by luciferase reporter gene assays, miR-133a bound to XIST and the 3'UTR of EGFR by direct targeting.

LncRNA XIST Promotes Pancreatic Cancer Proliferation through miR-133a/EGFR

Furthermore, an inverse relationship between lncRNA XIST and miR-101 was found. Polycomb group protein enhancer of zeste homolog 2 (EZH2), a direct target of miR-101, could mediated the biological effects that lncRNA XIST exerted.

Long non-coding RNA XIST regulates gastric cancer progression by acting as a molecular sponge of miR-101 to modulate EZH2 expression

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

LncRNA XIST also contributed to GC cell invasion both in vitro and in vivo. We revealed that XIST functioned as competing endogenous RNA to repress miR-497, which controlled its down-stream target MACC1.

Long non-coding RNA XIST promotes cell growth and invasion through regulating miR-497/MACC1 axis in gastric cancer

MAPK signaling pathway；Neurotrophin signaling pathway；GnRH signaling pathway； HTLV-I infection

Finally, lncRNA-Xist knockdown and miR-103a overexpression independently down-regulated MAP3K3 pathway.

Long non-coding RNA Xist promotes progression of non-small-cell lung cancer (NSCLC) by modulating miR-103a and MAP3K3 pathway

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.

HIF-1 signaling pathway；T cell receptor signaling pathway；Fc epsilon RI signaling pathway；Neurotrophin signaling pathway；Toxoplasmosis；Hepatitis C；Proteoglycans in cancer

In addition, we revealed that there was reciprocal repression between XIST and miR-139-5p. PDK1 was identified as a direct target of miR-139-5p.

Long non-coding RNA XIST promotes cell growth by regulating miR-139-5p/PDK1/AKT axis in hepatocellular carcinoma

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

MiR-181a was up-regulated in HCC tissues and its expression level in metastatic HCC tissues was much higher than in non-metastasis samples. PTEN was found to be a target gene of miR-181a. MiR-181a had multiple binding sites with the long non-coding RNA (lncRNA) XIST.

Long non-coding RNA XIST regulates PTEN expression by sponging miR-181a and promotes hepatocellular carcinoma progression

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

In particular, our results suggested that lncRNA-XIST may act as a competitive endogenous RNA, effectively becoming a sink for miR-494, leading to derepression of its target gene, phosphatase and tensin homolog deleted on chromosome ten (PTEN). In addition, an inverse relationship between lncRNA-XIST and miR-494 was observed in spinal cord tissues of SCI rats. Further study demonstrated that antagomiR-494 could reverse the protective effects of lncRNA-XIST knockdown on SCI rats through blocking the PTEN/PI3K/AKT signaling pathway.

Long Coding RNA XIST Contributes to Neuronal Apoptosis through the Downregulation of AKT Phosphorylation and Is Negatively Regulated by miR-494 in Rat Spinal Cord Injury

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

In particular, our results suggested that lncRNA-XIST may act as a competitive endogenous RNA, effectively becoming a sink for miR-494, leading to derepression of its target gene, phosphatase and tensin homolog deleted on chromosome ten (PTEN).

Long Coding RNA XIST Contributes to Neuronal Apoptosis through the Downregulation of AKT Phosphorylation and Is Negatively Regulated by miR-494 in Rat Spinal Cord Injury

Chemokine signaling pathway；VEGF signaling pathway；Focal adhesion；Leukocyte transendothelial migration；Regulation of actin cytoskeleton；Bacterial invasion of epithelial cells；Viral carcinogenesis；Proteoglycans in cancer

Meanwhile, miR-137 was negatively correlated with PXN expression while XIST was positively correlated with PXN expression. More importantly, XIST positively regulated PXN levels by sponging miR-137 in vitro and in vivo. Collectively, our study provided the evidence for the cross-talk between XIST, miR-137, and PXN, shedding light on the therapy for NSCLC.

Knockdown of long non-coding RNA XIST inhibits cell viability and invasion by regulating miR-137/PXN axis in non-small cell lung cancer

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

Endocytosis；TGF-beta signaling pathway；Hippo signaling pathway

Functionally, miR-92b could promote cell proliferation and metastasis of HCC in vitro and in vivo. Mechanistic investigations suggested that Smad7, which exhibited an inverse relationship with miR-92b expression in HCC, was a direct target of miR-92b and could reverse its effects on HCC tumorigenesis. Furthermore, long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) and miR-92b could directly interact with and repress each other, and XIST could inhibit HCC cell proliferation and metastasis by targeting miR-92b.

MicroRNA-92b promotes hepatocellular carcinoma progression by targeting Smad7 and is mediated by long non-coding RNA XIST

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