Breast cancer risk is associated with the HULC rs7763881, MTMR3 rs12537 polymorphisms, and serum levels of HULC and MTMR3 in Egyptian patients

Mol Biol Rep. 2023 Dec;50(12):10073-10081. doi: 10.1007/s11033-023-08897-1. Epub 2023 Nov 1.

Abstract

Background: Highly upregulated in liver cancer (HULC) is one of the LncRNAs that was documented to enhance cancer progression, and its downregulation is associated with cell cycle arrest and apoptosis. Myotubularin-related protein 3 (MTMR3) is required for autophagy, and many studies consider MTMR3 to be a negative regulator of autophagy processes. However, nothing is understood about how they regulate breast cancer.

Material and methods: This case-control study included 245 patients (Group A: 85 early BC Group B: 40 metastatic BC cases, Group C: 40 fibroadenoma cases; and Group D: 80 age matched healthy control subjects. TaqMan Real-time PCR was used to analyse rs7158663 and rs12537. MTMR3 and HULC gene expression levels were measured using RT-PCR.

Result: Breast cancer patients exhibited elevated serum MTMR3 and HULC compared to fibroadenomas and control cases. The MTMR3 rs12537 "T/T" genotype was highly expressed in cases of breast cancer (early and metastatic) compared to controls (risk genotype). On the other hand, the HULC rs7158663 genotypes were not statistically associated with breast cancer. However, when compared to the control, the C/C genotype of the HULC gene is higher in the case.MTMR3 gene expression was higher in the T/T genotype compared to both the C/C and C/T genotypes, while HULC gene expression was lower in the A/C genotype compared to both the A/A and C/C genotypes. Positive correlation between MTMR3 and HULC. MTMR3 and ALT, as well as HULC and alkaline phosphatase, both showed a statistically significant positive correlation.

Conclusion: Our findings reveal that MTMR3 and HULC serum expression and their SNPs (HULC rs7763881, MTMR3 rs12537) are associated with a higher risk for the development of breast cancer in the Egyptian population.

Keywords: Breast cancer; HULC; LncRNAs; MTMR3; Polymorphism.

MeSH terms

  • Breast Neoplasms* / genetics
  • Case-Control Studies
  • Egypt
  • Female
  • Genotype
  • Humans
  • Liver Neoplasms* / genetics
  • Protein Tyrosine Phosphatases, Non-Receptor / genetics
  • RNA, Long Noncoding* / genetics

Substances

  • MTMR3 protein, human
  • Protein Tyrosine Phosphatases, Non-Receptor
  • RNA, Long Noncoding
  • HULC long non-coding RNA, human