Breast cancer has become the most commonly diagnosed cancer. Heterogeneous nuclear ribonucleoprotein C (HNRNPC), a reader of N6-methyladenosine (m6A), has been observed to be upregulated in various types of cancer. Nevertheless, the role of HNRNPC in breast cancer and whether it is regulated by m6A modification deserve further investigation. The expression of HNRNPC in breast cancer was examined by quantitative real-time polymerase chain reaction and western blot analysis. RNA immunoprecipitation was performed to validate the binding relationships between HNRNPC and WD repeat domain 77 (WDR77). The effects of HNRNPC and m6A regulators on WDR77 were investigated by actinomycin D assay. The experiments in vivo were conducted in xenograft models. In this research, we found that HNRNPC was highly expressed in breast cancer, and played a crucial role in cell growth, especially in the luminal subtype. HNRNPC could combine and stabilize WDR77 mRNA. WDR77 successively drove the G1/S phase transition in the cell cycle and promoted cell proliferation. Notably, this regulation axis was closely tied to the m6A modification status of WDR77 mRNA. Overall, a critical regulatory mechanism was identified, as well as promising targets for potential treatment strategies for luminal breast cancer.

中文翻译：

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HNRNPC 通过 m6A 依赖性方式稳定 WDR77 mRNA 促进雌激素受体阳性乳腺癌细胞周期

乳腺癌已成为最常诊断的癌症。异质核核糖核蛋白 C (HNRNPC) 是 N6-甲基腺苷 (m6A) 的读者，已被观察到在各种类型的癌症中表达上调。尽管如此，HNRNPC在乳腺癌中的作用以及它是否受到m6A修饰的调节值得进一步研究。通过实时定量聚合酶链反应和蛋白质印迹分析检测乳腺癌中 HNRNPC 的表达。进行 RNA 免疫沉淀以验证 HNRNPC 和 WD 重复结构域 77 (WDR77) 之间的结合关系。通过放线菌素 D 测定研究了 HNRNPC 和 m6A 调节剂对 WDR77 的影响。体内实验是在异种移植模型中进行的。在这项研究中，我们发现HNRNPC在乳腺癌中高表达，并且在细胞生长中发挥着至关重要的作用，尤其是在管腔亚型中。 HNRNPC 可以结合并稳定 WDR77 mRNA。 WDR77先后驱动细胞周期G1/S期转变，促进细胞增殖。值得注意的是，该调节轴与 WDR77 mRNA 的 m6A 修饰状态密切相关。总体而言，确定了一个关键的调节机制，以及管腔乳腺癌潜在治疗策略的有希望的目标。