ArticleCellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology2020
Genistein Represses HOTAIR/Chromatin Remodeling Pathways to Suppress Kidney Cancer.
Article in Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Unveiling the functional paradigm of exosome-derived long non-coding RNAs (lncRNAs) in cancer: based on a narrative review and systematic review.Journal of cancer research and clinical oncology · 2023Pooled it
- lncRNA HOTAIR in Cancer: Recent Advances and Critical Perspectives on Molecular Mechanisms.Cancer management and research · 2026Review
- Cardiovascular protective effects of natural flavonoids on intestinal barrier injury.Molecular and cellular biochemistry · 2025Review
- Natural Compounds in Cancer Therapy: Revealing the Role of Flavonoids in Renal Cell Carcinoma Treatment.Biomolecules · 2025Review
- Isoflavones: Promising Natural Agent for Cancer Prevention and Treatment.Food science & nutrition · 2025Review
- Review
- Molecular pharmacology of the onco-TRP channel TRPV6.Channels (Austin, Tex.) · 2023Review
- Structural mechanism of human oncochannel TRPV6 inhibition by the natural phytoestrogen genistein.Nature communications · 2023Article
- Mutual Regulation of ncRNAs and Chromatin Remodeling Complexes in Normal and Pathological Conditions.International journal of molecular sciences · 2023Review
- RNAsmc: A integrated tool for comparing RNA secondary structure and evaluating allosteric effects.Computational and structural biotechnology journal · 2023Article
- Genistein-induced mitochondrial dysfunction and FOXO3a/PUMA expression in non-small lung cancer cells.Pharmaceutical biology · 2022Article
- Contribution of Non-Coding RNAs to Anticancer Effects of Dietary Polyphenols: Chlorogenic Acid, Curcumin, Epigallocatechin-3-Gallate, Genistein, Quercetin and Resveratrol.Antioxidants (Basel, Switzerland) · 2022Review
- Effects of Genistein on Common Kidney Diseases.Nutrients · 2022Review
- The Role of m6A RNA Methylation in Cancer: Implication for Nature Products Anti-Cancer Research.Frontiers in pharmacology · 2022Review
- Genistein in the Treatment of Hypertension: A Review.Endocrine, metabolic & immune disorders drug targets · 2022Review
- Targeting lncRNAs of colorectal cancers with natural products.Frontiers in pharmacology · 2022Review
- The protective activity of genistein against bone and cartilage diseases.Frontiers in pharmacology · 2022Review
- Long noncoding RNACell adhesion & migration · 2021Article
- Dietary Phytoestrogens and Their Metabolites as Epigenetic Modulators with Impact on Human Health.Antioxidants (Basel, Switzerland) · 2021Review
- A putative role for lncRNAs in epigenetic regulation of memory.Neurochemistry international · 2021Review
Corrections and comments
- Erratum issuedErratum.2020
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND/
aimsGenistein, a soy isoflavone, has been shown to have anti-cancer effects in various cancers including renal cancer. Long non-coding RNA, HOX transcript antisense RNA (HOTAIR), is involved in cancer progression and metastasis, such as renal cancer. Our aim was to investigate the effects of genistein on HOTAIR chromatin remodeling functions.
methodsWe used MTS assays and Transwell migration assays to study the effects of genistein on cell proliferation and migration respectively in human renal cell carcinoma (RCC) cell lines. We used Western blots to analyze SNAIL and ZO-1 expression. We performed chromatin immunoprecipitation (ChIP) assays to study recruitment of the polycomb repressive complex 2 (PRC2) to the ZO-1 promoter. We performed RNA immunoprecipitation (RIP) assays to study interaction between HOTAIR and PRC2, SMARCB1 or ARID1A. We also performed transfection experiments to overexpress EED, HOTAIR and knockdown SMARCB1.
resultsGenistein reduced cell proliferation and migration of human renal cell carcinoma cell lines. ChIP assays indicated that genistein reduces recruitment of the PRC2 to the ZO-1 promoter and increased its expression. RIP assays showed that genistein inhibits HOTAIR interaction with PRC2, leading to tumor suppression. Immunoprecipitation also revealed that genistein reduced EED levels in PRC2, suggesting that decreased EED levels suppress HOTAIR interaction with PRC2. EED overexpression in the presence of genistein restored PRC2 interaction with HOTAIR and reduced ZO-1 transcription, suggesting genistein activates ZO-1 by inhibiting HOTAIR/PRC2 functions. RIP assays also showed that HOTAIR interacts with SMARCB1 and ARID1A, subunits of the human SWI/SNF chromatin remodeling complex and genistein reduces this interaction. Combination of HOTAIR overexpression and SMARCB1 knockdown in the presence of genistein revealed that genistein inhibits SNAIL transcription via the HOTAIR/SMARCB1 pathway.
conclusionGenistein suppresses EED levels in PRC2 and inhibits HOTAIR/PRC2 interaction. Genistein suppresses HOTAIR/PRC2 recruitment to the ZO-1 promoter and enhances ZO-1 transcription. Genistein also inhibits SNAIL transcription via reducing HOTAIR/SMARCB1 interaction. We demonstrate that the reduction of HOTAIR interaction with chromatin remodeling factors by genistein represses HOTAIR/chromatin remodeling pathways to suppress RCC malignancy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.