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Journal Article Ppublish 1 citation

PubMed: 39891867 DOI: 10.1007/s10549-024-07603-4

Molecular Dynamics of Breast Cancer Subtypes: The Role of FAM83H-AS1 Long Non-coding RNA in Breast Cancer Metastasis.

Breast Cancer Res Treat 210(3):645-659

Authors: Mohammad Hossein Hashemi, Hassan Moaiery, Bahram Nikkhoo, Fatemeh Zamani, Soma Mahmoodian, Marzieh Soheili, Farzad Soleimani, Zhila Bahramirad, MohammadBagher KhademErfan, Bayazid Ghaderi, Mohammad Erfan Keyhani, Sherko Nasseri

Affiliations

  • Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, 6617957146, Iran.
  • Department of Surgery, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.
  • Department of Pathology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.
  • Lung Diseases and Allergy Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran.
  • Department of Epidemiology and Biostatistics, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.
  • College of Pharmacy, Western New England University, Springfield, MA, USA.
  • Cancer & Immunology Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.
  • Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, 6617957146, Iran.
  • Cancer & Immunology Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.
  • Department of Molecular Medicine and Medical Biotechnology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.

Abstract

PURPOSE

Breast cancer is the leading cause of cancer-related deaths in women. Long non-coding RNAs (lncRNAs) play an important role in gene regulation and are emerging as major players in cancer biology, This study investigates the expression of FAM83H-AS1 in breast cancer and its association with tumor grade, hormone receptors, pathological diagnosis, and molecular markers related to epithelial-mesenchymal transition (EMT).

METHODS

The expression of the long non-coding RNA FAM83H-AS1 in 80 breast cancer patients was assessed using quantitative real-time PCR (qRT-PCR). Clinical significance was evaluated through histopathological and immunohistochemical analyses. The associations of FAM83H-AS1 expression with tumor grade, hormone receptor status, and epithelial-mesenchymal transition (EMT) markers were analyzed.

RESULTS

A positive correlation was observed between tumor grade and the expression of FAM83H-AS1, N-cadherin, E-cadherin, and vimentin, whereas FGF-18, TGF-β, and β-catenin were downregulated. Estrogen receptor positivity was associated with CLDN1 and Snail-1 expression, while HER2 positivity was linked to vimentin expression. Snail-1 expression correlated positively with Ki-67 levels. All genes except MMP2 were significantly associated with lymph node metastasis. Comparative analysis revealed significant differences in FGF-18, TGF-β, N-cadherin, β-catenin, and MMP2 expression among luminal A, luminal B, and triple-negative breast cancer (TNBC) subtypes. FAM83H-AS1 was upregulated in TNBC compared to luminal A and inflammatory breast cancer (IBC), although the difference was not statistically significant. TNBC Exhibited upregulation of TGF-β, N-cadherin, and β-catenin, suggesting their role in the aggressive nature of this subtype. In contrast, MMP2 was downregulated in TNBC compared to IBC, potentially indicating a suppressive role in tumor invasion in TNBC. Vimentin was upregulated in IBC compared to luminal A, indicating its involvement in IBC's aggressive behavior. MMP2 and MMP9 were significantly upregulated in IBC compared to luminal A.

CONCLUSION

FAM83H-AS1 shows potential as a prognostic biomarker and therapeutic target, especially in TNBC and IBC, with implications for personalized breast cancer treatment strategies. Its expression correlates with tumor grade, hormone receptor status, and EMT markers, suggesting a role in cancer progression and metastasis.

MeSH

Genes, Catenins, Vimentin, Breast Neoplasms, Epithelial-Mesenchymal Transition, Neoplasms, Inflammatory Breast Neoplasms, Cadherins, Hormones, Rna, Untranslated, Neoplasm Metastasis, Breast, Therapeutics, Rna, Long Noncoding, Rna