Lnc RNA HOTAIR functions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer

Abstract

BackgroundAccumulating evidence indicates that the long non-coding RNA HOTAIR plays a critical role in cancer progression and metastasis. However, the overall biological role and clinical significance of HOTAIR in gastric carcinogenesis remains largely unknown.MethodsHOTAIR expression was measured in 78 paired cancerous and noncancerous tissue samples by real-time PCR. The effects of HOTAIR on gastric cancer cells were studied by overexpression and RNA interference approaches in vitro and in vivo. Insights of the mechanism of competitive endogenous RNAs (ceRNAs) were gained from bioinformatic analysis, luciferase assays and RNA binding protein immunoprecipitation (RIP). The positive HOTAIR/HER2 interaction was identified and verified by immunohistochemistry assay and bivariate correlation analysis.ResultsHOTAIR upregulation was associated with larger tumor size, advanced pathological stage and extensive metastasis, and also correlated with shorter overall survival of gastric cancer patients. Furthermore, HOTAIR overexpression promoted the proliferation, migration and invasion of gastric carcinoma cells, while HOTAIR depletion inhibited both cell invasion and cell viability, and induced growth arrest in vitro and in vivo. In particular, HOTAIR may act as a ceRNA, effectively becoming a sink for miR-331-3p, thereby modulating the derepression of HER2 and imposing an additional level of post-transcriptional regulation. Finally, the positive HOTAIR/HER2 correlation was significantly associated with advanced gastric cancers.ConclusionsHOTAIR overexpression represents a biomarker of poor prognosis in gastric cancer, and may confer malignant phenotype to tumor cells. The ceRNA regulatory network involving HOTAIR and the positive interaction between HOTAIR and HER2 may contribute to a better understanding of gastric cancer pathogenesis and facilitate the development of lncRNA-directed diagnostics and therapeutics against this disease.

HOTAIR Epigenetically Modulates PTEN Expression via MicroRNA-29b: A Novel Mechanism in Regulation of Liver Fibrosis

“…As confirmed by situ hybridization assay, HOTAIR was distributed in both nucleus and cytoplasm 33 , and has been reported to be able to bind miRNAs in cancers. 31,34 In this study, it was found that loss of DNMT3b inhibited HOTAIR-induced PTEN methylation. In addition, lack of the miR-29b binding site in HOTAIR prevented the suppression of miR-29b expression.…”

Long noncoding RNA-HOTAIR affects chemoresistance by regulating HOXA1 methylation in small cell lung cancer cells

“…To stably silence endogenous HOTAIR, two shRNA oligonucleotides were purchased from Sigma Aldrich (Shanghai, China), and the oligonucleotides were as follows: shHOTAIR-I: 5′-CACCGCCTTTGCTTCGTGCTGATTCCGAAGAATCAG CACGAAGCAAAGGC-3′ and 5′-AAAAGCCTTTGCTTCGT GCTGATTCTTCGGAATCAGCACACGAAGCAAAGGC-3′; 11 shHOTAIR-II: 5′-GATCCCGAACGGGAGTACAGAGAGATT CAAGAGATCTCTCTGTACTCCCGTTCTTTTTTGGAAA-3′ and 5′-CGCGTTTCCAAAAAAGAACGGGAGTACAGAGAG ATCTCTTGAATCTCTCTGTACTCCCGTTCGG-3′; 12 they were cloned into the pGCSi-neo-GFP vector to generate pGCSi-neo-GFP-HOTAIR-RNAi(s). SCLC cells were transfected with shRNA via Lipofectamine 2000 (Invitrogen).…”

“…9 In NSCLC, SULF2 and IGFBP-3 have also been observed to affect drug sensitivity of NSCLC cells. [10][11][12] The HOX family, including 39 HOX genes, is divided into four groups (A-D) in tightly linked clusters on different chromosomes, and has the equivalent position in each cluster. HOXA1, one of the HOX family members, has been reported to be involved in many important biological processes including cell growth, apoptosis, transformation, and survival.…”

Long Noncoding RNA in Digestive Tract Cancers: Function, Mechanism, and Potential Biomarker

“…In GC, HOTAIR-expressing GC cells exhibited an enhanced ability of metastasis and peritoneal dissemination in a nude mouse model [57]. Liu et al confirmed that HOTAIR was markedly increased in GC tissues compared with matched normal tissues, and its loss led to suppressed proliferation of GC cells in vitro and in vivo.The investigation of the molecular mechanism revealed that HOTAIR indirectly regulated human epithelial growth factor receptor 2 (HER2) by competitively binding to miR-331-3p [58]. In addition, the plasma levels of HOTAIR were increased in the patients with GC compared with the healthy controls [52], suggesting that HOTAIR may be a noninvasive biomarker for GC diagnosis.…”