Reactivation of HIC-1 gene by saRNA inhibits clonogenicity and invasiveness in breast cancer cells

Zhao, Feng; Pan, Shengli; Gu, Yu; Guo, Shanyu; Dai, Qiancheng; Yu, Yingyan; Zhang, Wei

doi:10.3892/ol.2014.2633

Cited by 4 publications

(2 citation statements)

References 26 publications

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“…ERBB2 is located in chromosome 17q21.2, where some common oncogenes or tumor suppressor genes, such as TOP2A, TAU, p53, and HIC-1 are located ( Zhang and Yu, 2011 ). Our previous studies confirmed that re-activation of tumor suppressor HIC-1 by small-activating RNAs inhibits cell division, growth and invasion ( Zhao et al, 2014 , 2015 ). Retinoic acid receptor alpha (RARA) is another gene located on chromosome 17q21.2.…”

Section: Introductionsupporting

confidence: 82%

Cross-Database Analysis Reveals Sensitive Biomarkers for Combined Therapy for ERBB2+ Gastric Cancer

et al. 2018

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Exploring ERBB2-related pathways will help us finding sensitive molecules and potential combined therapeutic targets of ERBB2-targeted therapy for ERBB2+ gastric cancer (GC). In this study, we performed a cross-databases study focused on ERBB2+ GC. The data of ERBB2+ GC deposited in the cancer genome atlas (TCGA), gene expression omnibus (GEO), InBio MapTM, cancer cell line encyclopedia (CCLE), and cancer therapeutics response portal (CTRP) were analyzed. The correlation of expression levels of candidate and IC50 of candidate genes-targeted drugs were verified on NCI-N87 and MKN-45 GC cell lines. We found that RARA, THRA, CACNB1, and TOP2A are drug sensitive biomarkers of ERBB2-targeted treatment with FDA-approved drugs. All these genes act through Myc signaling pathway. Myc is the downstream hub gene of both ERBB2 and RARA. The expression of RARA, THRA, and CACNB1 were negatively correlated with Myc activation, while ERBB2 and TOP2A positively correlated with Myc activation. SH3BGRL3, SH3BGRL, and NRG2 were identified as potential ligands of ERBB2. The ERBB2+ GC with RARA amplification demonstrated better prognosis than those without RARA amplification, while overexpression of NRG2 and SH3BGRL correlated with poor prognosis in ERBB2+ GC. About 90% of ERBB2+ GC was compatible with chromosome instability (CIN) subtype of TCGA, which overlaps with intestinal-type GC in Lauren classification. In validating experiments, combination of Lapatinib and all-trans retinoic acid (ATRA) synergistically suppresses cell growth, and accompanied by decreased expression of MYC. In conclusions, we identified several predicting biomarkers for ERBB2-targeted therapy and corresponding histological features of ERBB2+ GC. Combination of ERBB2 antagonist or RARA agonist may be effective synergistic regimens for ERBB2+ GC.

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Section: Introductionsupporting

confidence: 82%

Cross-Database Analysis Reveals Sensitive Biomarkers for Combined Therapy for ERBB2+ Gastric Cancer

et al. 2018

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“…Although studies have identified HIC-1 as having frequent changes in hypermethylation or loss of heterozygosity in many human cancers [ 40 , 41 ], the molecular mechanisms through which HIC-1 inhibits cancer progression remain poorly understood. HIC-1 is a multifunctional, sequence-specific transcriptional repressor that interacts with several major repression and chromatin remodeling complexes [ 42 , 43 ]. To date, many studies have showed that the IL-6/Janus kinase/STAT3 signaling pathways are involved in drug resistance, angiogenesis, migration, and other processes in cancers [ 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

Downregulation of hypermethylated in cancer-1 by miR-4532 promotes adriamycin resistance in breast cancer cells

et al. 2018

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BackgroundMicroRNAs are small RNAs (~ 22 nt) that modulate the expression of thousands of genes in tumors and play important roles in the formation of multidrug resistance. In this study, we firstly investigated that miR-4532 involved in the multidrug resistance formation of breast cancer by targeting hypermethylated in cancer 1 (HIC-1), a tumor-suppressor gene.MethodsTo identify and characterize the possible miRNAs in regulating multidrug resistance, we employed the transcriptome sequencing approach to profile the changes in the expression of miRNAs and their target mRNAs were obtained by bioinformatics prediction. Then the molecular biology experiments were conducted to confirm miR-4532 involved in multidrug resistance formation of breast cancer.ResultsThe luciferase reporter assay experiment was employed to confirm that HIC-1 was the target of miR-4532. Transfection with an miR-4532 mimic indicated miR-4532 mimic significantly increased breast cancer cell resistance to adriamycin. Cell proliferation and invasion assay experiments showed overexpression of HIC-1 inhibited the invasion and metastasis of breast cancer cells. Meanwhile, the interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3) signaling pathway was confirmed to be involving in multidrug resistance by western blotting experiments.ConclusionsThese results suggest that downregulation of hypermethylated in cancer-1 by miR-4532 could promote adriamycin resistance in breast cancer cells, in which the IL-6/STAT3 pathway was regulated by the HIC-1. This finding might contribute to new therapeutic target for reversal of tumor resistance.Electronic supplementary materialThe online version of this article (10.1186/s12935-018-0616-x) contains supplementary material, which is available to authorized users.

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SaRNA-mediated activation of TRPV5 reduces renal calcium oxalate deposition in rat via decreasing urinary calcium excretion

et al. 2017

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Hypercalciuria is a main risk factor for kidney stone formation. TRPV5 is the gatekeeper protein for mediating calcium transport and reabsorption in the kidney. In the present study, we tested the effect of TRPV5 activation with small activating RNA (saRNA), which could induce gene expression by targeting the promoter of the gene, on ethylene glycol (EG)-induced calcium oxalate (CaOx) crystals formation in rat kidney. Five pairs of RNA activation sequences targeting the promoter of rat TRPV5 were designed and synthesized. The synthesized saRNA with the strongest activating effect was selected, and transcellular calcium transportation was tested by Fura-2 analysis. Subsequently, Sprague-Dawley rats were equally divided into three groups and fed with water, 1% EG for 28 days after injecting the negative control saRNA, 1% EG for 28 days after injecting the selected TRPV5-saRNA, respectively. The CaOx crystal formation and the 24-h urine components were assessed. In vitro study, saRNA ds-320 could significantly activate the expression of TRPV5 and transcellular calcium transportation. In vivo study, after 28 days treatment of EG, rats pre-infected with saRNA ds-320 had lower urinary calcium excretion and renal CaOx crystals formation as compared to that pre-infected with negative control saRNA. Activation of TRVP5 with saRNA ds-320 could inhibit EG-induced calcium oxalate crystals formation via promoting urine calcium reabsorption and decreasing urine calcium excretion in rats.

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Reactivation of HIC-1 gene by saRNA inhibits clonogenicity and invasiveness in breast cancer cells

Cited by 4 publications

References 26 publications

Cross-Database Analysis Reveals Sensitive Biomarkers for Combined Therapy for ERBB2+ Gastric Cancer

Cross-Database Analysis Reveals Sensitive Biomarkers for Combined Therapy for ERBB2+ Gastric Cancer

Downregulation of hypermethylated in cancer-1 by miR-4532 promotes adriamycin resistance in breast cancer cells

SaRNA-mediated activation of TRPV5 reduces renal calcium oxalate deposition in rat via decreasing urinary calcium excretion

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