Chemokine signaling pathway；MAPK signaling pathway；Endocytosis；Axon guidance；Epithelial cell signaling in Helicobacter pylori infection；Viral carcinogenesis；Neurotrophin signaling pathway；Bacterial invasion of epithelial cells；Renal cell carcinoma；Shigellosis；Salmonella infection；Pancreatic cancer；VEGF signaling pathway；Focal adhesion；Pathways in cancer；Pathogenic Escherichia coli infection；Adherens junction；Tight junction；GnRH signaling pathway；Regulation of actin cytoskeleton；T cell receptor signaling pathway；Fc gamma R-mediated phagocytosis；Leukocyte transendothelial migration；Proteoglycans in cancer

In this study we identified long non-coding RNA (lncRNA) MALAT1 can function as a ceRNA of cell division cycle 42 (cdc42) 3'UTR in inducing migration and invasion of breast cancer cells via miR-1. We found that miR-1 bound both MALAT1 and cdc42 3'UTR directly.

MALAT1 induced migration and invasion of human breast cancer cells by competitively binding miR-1 with cdc42

Tight junction；Cell cycle；p53 signaling pathway；Bladder cancer；Non-small cell lung cancer；PI3K-Akt signaling pathway；T cell receptor signaling pathway；Hepatitis B；Melanoma；Glioma；Measles；HTLV-I infection；Pathways in cancer；Small cell lung cancer；Viral carcinogenesis；Pancreatic cancer；Chronic myeloid leukemia

Furthermore, MALAT1 acted as an endogenous potent regulator by directly binding to miR-124 and down-regulating miR-124 expression. In addition, MALAT1 reversed the inhibitory effect of miR-124 on breast cancer proliferation and was involved in the cyclin-dependent kinase 4 (CDK4) expression.

miR-124 downregulation leads to breast cancer progression via LncRNA-MALAT1 regulation and CDK4/E2F1 signal activation

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

Moreover, the present study elucidated the MALAT1-miR-124-CDK4/E2F1 signaling pathway in breast cancer, which might provide a new approach for tackling breast cancer.

miR-124 downregulation leads to breast cancer progression via LncRNA-MALAT1 regulation and CDK4/E2F1 signal activation

Cell cycle；TGF-beta signaling pathway

Taken together, our findings indicated that SNHG16 induces breast cancer cell migration by competitively binding miR-98 with E2F5, and SNHG16 can serve as a potential therapeutic target for breast cancer treatment.

SNHG16 contributes to breast cancer cell migration by competitively binding miR-98 with E2F5

In our research, lncRNA-NEAT1 was specifically upregulated in BC cell lines and promoted BC cell growth through targeting miR-101. Knockdown of NEAT1 inhibited the proliferation and DNA synthesis of human BC cell in vitro. In addition, the regulation of EZH2 by miR-101 was required in NEAT1 induced BC cell growth. These findings indicated that NEAT1 might suppress the tumor growth via miR-101 dependent EZH2 regulation.

The long non-coding RNA NEAT1 interacted with miR-101 modulates breast cancer growth by targeting EZH2

In our research, lncRNA-NEAT1 was specifically upregulated in BC cell lines and promoted BC cell growth through targeting miR-101. Knockdown of NEAT1 inhibited the proliferation and DNA synthesis of human BC cell in vitro. In addition, the regulation of EZH2 by miR-101 was required in NEAT1 induced BC cell growth. These findings indicated that NEAT1 might suppress the tumor growth via miR-101 dependent EZH2 regulation.

The long non-coding RNA NEAT1 interacted with miR-101 modulates breast cancer growth by targeting EZH2

Furthermore, we demonstrated that one miRNA, miR-29a-5p, can bind to both the XIAP and FSCN1 3'UTRs and play an important role in that interactions.

XIAP 3'-untranslated region as a ceRNA promotes FSCN1 function in inducing the progression of breast cancer by binding endogenous miR-29a-5p

Transcriptional misregulation in cancer

In addition, the RNA-binding protein fused in sarcoma/translocated in liposarcoma (FUS/TLS) physically interacted with NEAT1, and reducing the expression of FUS/TLS also induced cell apoptosis. Multiple miRNAs were identified as regulators of NEAT1, but only overexpression of miR-548ar was able to decrease NEAT1 expression and promote apoptosis.

NEAT1 is Required for Survival of Breast Cancer Cells Through FUS and miR-548

HIF-1 signaling pathway；mTOR signaling pathway；Pathways in cancer；Proteoglycans in cancer；Renal cell carcinoma

The upregulated UCA1 sponges miR-18a, which is a negative regulator of HIF1α. Therefore, UCA1 upregulation is further enhanced through a miR-18a-HIF1α feedback loop.

Long non-coding RNA UCA1 enhances tamoxifen resistance in breast cancer cells through a miR-18a-HIF1α feedback regulatory loop

KDM5B-silencing in the TNBC cells correlated with the upregulation of hsa-miR-448 and led to suppression of MALAT1 expression with decreased migration, invasion and clonogenic capacity in vitro, as well as, poor survival in vivo.

Aberrant KDM5B expression promotes aggressive breast cancer through MALAT1 overexpression and downregulation of hsa-miR-448

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

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

GAS5 suppresses cancer proliferation by acting as a molecular sponge for miR-21, leading to the de-repression of phosphatase and tensin homologs (PTEN), the endogenous target of miR-21.

Downregulation of LncRNA GAS5 causes trastuzumab resistance in breast cancer

Hippo signaling pathway；Adherens junction

In addition, our findings demonstrate a reciprocal negative control relationship between MALAT1 and miR-1: downregulation of MALAT1 increased expression of microRNA-1 (miR-1), while overexpression of miR-1 decreased MALAT1 expression. Slug was identified as a direct target of miR-1. We proposed that MALAT1 exerted its function through the miR-1/slug axis.

Reciprocal regulation of Hsa-miR-1 and long noncoding RNA MALAT1 promotes triple-negative breast cancer development

Hippo signaling pathway

Moreover, full-length HOTAIR transcriptionally inhibits miR-34a specifically, leading to upregulation of Sox2, which is targeted by miR-34a.

Long Non-Coding RNA HOTAIR Regulates the Proliferation, Self-Renewal Capacity, Tumor Formation and Migration of the Cancer Stem-Like Cell (CSC) Subpopulation Enriched from Breast Cancer Cells

Transcriptional misregulation in cancer

Compared with the MCF7 cells, the MCF7-ROR cells had remarkably higher proliferation rates, down-regulated E-cadherin and miR-205 expressions, as well as increased vimentin, invasive ability, and mRNA expression of ZEB1 and ZEB2. Compared with the MCF7/TR5 and MDA-MB-231 cells, up-regulated E-cadherin and miR-205 expression, down-regulated expression of vimentin, ZEB1, and ZEB2 mRNA, and decreased invasive ability were observed in the MCF7/TR5 ROR-siRNA and MDA-MB-231 ROR-siRNA cells.

Effects of long noncoding RNA-ROR on tamoxifen resistance of breast cancer cells by regulating microRNA-205

Specifically, linc-ROR prevented the degradation of mir-205 target genes, including the EMT inducer ZEB2.

LincRNA-ROR induces epithelial-to-mesenchymal transition and contributes to breast cancer tumorigenesis and metastasis

Compared with the MCF7 cells, the MCF7-ROR cells had remarkably higher proliferation rates, down-regulated E-cadherin and miR-205 expressions, as well as increased vimentin, invasive ability, and mRNA expression of ZEB1 and ZEB2. Compared with the MCF7/TR5 and MDA-MB-231 cells, up-regulated E-cadherin and miR-205 expression, down-regulated expression of vimentin, ZEB1, and ZEB2 mRNA, and decreased invasive ability were observed in the MCF7/TR5 ROR-siRNA and MDA-MB-231 ROR-siRNA cells.

Effects of long noncoding RNA-ROR on tamoxifen resistance of breast cancer cells by regulating microRNA-205