The Potential Role of SNRPD1 Stabilized by IGF2BP2 in the Progression of Triple-Negative Breast Cancer.

Abstract

Background: Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), an RNA-binding protein with N6-methyladenosine (m6A) reader function, is associated with the poor prognosis of various tumors, including triple-negative breast cancer (TNBC). Small nuclear ribonucleoprotein D1 polypeptide (SNRPD1), a spliceosome member, exerts diagnostic and therapeutic functions in breast cancer by regulating the cell cycle and is a potential therapeutic target. However, the interaction between IGF2BP2 and SNRPD1 in the progression of TNBC remain unclear.

Objective: This study aimed to investigate the interaction between IGF2BP2 and SNRPD1 in TNBC and elucidate the underlying mechanisms.

Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the expression levels of SNRPD1 and IGF2BP2 in human normal breast cells (MCF10A) and TNBC cells (MDA-MB-231). MDA-MB-231 cells were transfected with SNRPD1 interference or overexpression vectors, or co-transfected with SNRPD1 interference and IGF2BP2 overexpression vectors simultaneously. Cell viability, apoptosis, and invasion were assessed using MTT, flow cytometry, and Transwell assays. RNA stability, m6A levels, and the interaction between SNRPD1 and IGF2BP2 were evaluated using qRT-PCR, methylated RNA immunoprecipitation, and RIP assays.

Results: SNRPD1 was significantly up-regulated in TNBC cells, promoting cell viability and invasion while inhibiting apoptosis. IGF2BP2 was also up-regulated in TNBC cells and enhanced SNRPD1 mRNA stability via m6A modification. Furthermore, IGF2BP2 overexpression reversed the anti-tumor effect of SNRPD1 knockdown.

Conclusion: IGF2BP2 and SNRPD1 were significantly highly expressed in TNBC cells. IGF2BP2 might enhance the stability and protein expression of SNRPD1 through m6A-dependent mechanisms, potentially contributing to the progression of TNBC.