What question did this study set out to answer?

The study investigates the role of YTHDC1 in promoting proliferation and stemness in triple-negative breast cancer cells by regulating BACH1 mRNA stability.

April 26, 2026

YTHDC1 promotes triple-negative breast cancer cell proliferation and stemness by regulating BACH1 mRNA stability in an m6A-dependent manner

Key Points

The study investigates the role of YTHDC1 in promoting proliferation and stemness in triple-negative breast cancer cells by regulating BACH1 mRNA stability.
In vitro assays including qRT-PCR, western blot, CCK-8, colony formation, and sphere formation were conducted.
Fluorescence in situ hybridization (FISH) and RNA immunoprecipitation (RIP) identified YTHDC1 binding sites on BACH1 mRNA.
Functional assays were performed to determine the effects of YTHDC1 silencing and BACH1 overexpression on TNBC cells.
YTHDC1 expression was significantly elevated in TNBC tissues and cells.
Silencing YTHDC1 inhibited TNBC cell proliferation, colony formation, and stemness marker expression (Nanog, Oct4, and SOX2).
BACH1 overexpression counteracted the reduced proliferation and stemness resulting from YTHDC1 silencing.

Abstract

Triple-negative breast cancer (TNBC) is an aggressive malignancy characterized by a high mortality rate and limited treatment options. The mechanism by which YTHDC1 contributes to TNBC progression remains to be investigated. To investigate the role of YTHDC1 in TNBC, we performed in vitro real-time quantitative polymerase chain reaction (qRT-PCR), western blot (WB), cell counting kit-8 (CCK-8), colony formation, and sphere formation assays to evaluate its impacts on TNBC cell proliferation and stemness. Fluorescence in situ hybridization (FISH) and RNA immunoprecipitation (RIP) were employed to identify the binding sites of YTHDC1 on BACH1 mRNA. The stability of BACH1 mRNA following actinomycin D (ActD) treatment was analyzed after YTHDC1 silencing. Additionally, functional assays assessed the ability of BACH1 overexpression to counteract the inhibitory effects of YTHDC1 silencing on TNBC cell proliferation and stemness. We found that YTHDC1 expression was significantly elevated in TNBC tissues and cells. Silencing YTHDC1 inhibited cell proliferation, colony formation and sphere formation, and reduced the expression of stemness markers (Nanog, Oct4, and SOX2). YTHDC1 silencing also inhibited BACH1 mRNA nuclear export, leading to an increased nucleoplasmic ratio of BACH1 mRNA. Mechanistic studies revealed that YTHDC1 and m6A modifications significantly enriched on BACH1 mRNA, while YTHDC1 silencing reduced its stability. Importantly, BACH1 overexpression rescued the inhibitory effects of YTHDC1 silencing on TNBC cell proliferation and stemness marker expression. Collectively, YTHDC1 regulates BACH1 expression in an m6A-dependent mechanism, contributing to TNBC progression. Implications: Our findings provide a rationale for further investigation of the YTHDC1/BACH1 axis as a potential therapeutic target in TNBC.

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