Functional Interaction among lncRNA HOTAIR and MicroRNAs in Cancer and Other Human Diseases

Abstract

LncRNAs are a class of non-coding RNAs mostly involved in regulation of cancer initiation, metastatic progression, and drug resistance, through participation in post-transcription regulatory processes by interacting with different miRNAs. LncRNAs are able to compete with endogenous RNAs by binding and sequestering miRNAs and thereby regulating the expression of their target genes, often represented by oncogenes. The lncRNA HOX transcript antisense RNA (HOTAIR) represents a diagnostic, prognostic, and predictive biomarker in many human cancers, and its functional interaction with miRNAs has been described as crucial in the modulation of different cellular processes during cancer development. The aim of this review is to highlight the relation between lncRNA HOTAIR and different microRNAs in human diseases, discussing the contribution of these functional interactions, especially in cancer development and progression.

Keywords: cancer progression; lncRNA HOTAIR; miRNAs.

Figure 1

Schematic representation of principal functional interactions between lncRNA HOTAIR and different microRNAs. HOTAIR/miR-34a interaction promotes tumor cell proliferation, migration, and invasion by induction of the transcription factor c- Myc, the cyclin-dependent kinases CDK4 and CDK6, and anti-apoptotic proteins Bcl2 and SIRT1 in breast, gastric, pancreatic, prostate, and colon cancers; HOTAIR/miR-217 interaction modulates cell proliferation, migration, invasion, and epithelial mesenchymal transition (EMT) by downregulation of tumor suppressor genes DACH1 and GPC-5, and the activation of JAK3/STAT3 and HIF-1α/AXL signaling pathways in lung, gastric, and kidney cancers and in osteosarcoma; HOTAIR/miR-204 interaction induces cell migration and angiogenesis by the tyrosine kinase FAK signaling pathway in breast and renal cancers; HOTAIR/MiR326 interaction promotes tumor cell growth, proliferation, migration, and chemoresistance by induction of the FGF1, MEK1/2, and PI3K/AKT/mTOR signaling pathways in lung, colon, and glioma cancers; HOTAIR/Mir-141 interaction reduces tumor cell proliferation and invasion by decreasing the cell-cycle gene SKA2 and anti-apoptotic gene ABL2, and inducing the metastasis suppressor gene PCDH10 in renal cancer and glioma; HOTAIR/Mir139a interaction promotes tumor cell proliferation, migration, invasion, metastasis, and drug resistance by induction of the receptor tyrosine kinase c-Kit and AKT signaling pathways in prostate cancer and myeloid leukemia; HOTAIR/Mir152 interaction induces tumor cell proliferation, migration, and invasion by modulation of the human leukocyte antigen G (HLA-G) and metalloproteinases expression in prostate and gastric cancer; HOTAIR/Mir454-3p interaction modulates tumor cells growth and proliferation by induction of the STAT3/cyclin D1 signaling pathway in gastric cancer and chondrosarcoma; HOTAIR/Mir613 promotes cell proliferation, invasion, and migration by modulation of the cell surface receptor notch3 signaling pathway in pancreatic cancer and retinoblastoma; HOTAIR/Mir130a increases tumor invasion and metastasis by inducing EMT and upregulates the transcription factor ZEB1 and the chemokine ligand CCL18 in ESCC and gallbladder cancers; HOTAIR/Mir218 promotes tumor cell growth, proliferation, and resistance to ionizing radiation by induction of cell cycle genes in breast and liver cancers; HOTAIR/Mir1 interaction induces cell survival, proliferation, and EMT by upregulation of the cancer metastasis gene YY1 in liver cancer and medulloblastoma; HOTAIR/Mir148a interaction increases cancer cell migration, invasion, metastasis, and EMT by inducing the Snail2 gene, Estradiol (E2)/G protein-coupled estrogen receptor 1 (GPER), and HLG-A axes in breast, cervical, and ESCC cancers; HOTAIR/Mir206 interaction promotes tumor growth, migration, invasion, and EMT by induction of cyclin D genes, anti-apoptotic gene Bcl-w, and chemokine ligand CCL2 in breast, ovarian, and colon cancers and medulloblastoma.