Molecular, Cellular, and Integrative Physiology Graduate Program, Michigan State University, East Lansing, MI 48824, USA.
Department of Physiology, Michigan State University, East Lansing, MI 48824, USA.
Int J Mol Sci. 2023 Mar 7;24(6):5086. doi: 10.3390/ijms24065086.
Cancer remains the second leading cause of death, accounting for approximately 20% of all fatalities. Evolving cancer cells and a dysregulated immune system create complex tumor environments that fuel tumor growth, metastasis, and resistance. Over the past decades, significant progress in deciphering cancer cell behavior and recognizing the immune system as a hallmark of tumorigenesis has been achieved. However, the underlying mechanisms controlling the evolving cancer-immune landscape remain mostly unexplored. Heterogeneous nuclear ribonuclear proteins (hnRNP), a highly conserved family of RNA-binding proteins, have vital roles in critical cellular processes, including transcription, post-transcriptional modifications, and translation. Dysregulation of hnRNP is a critical contributor to cancer development and resistance. HnRNP contribute to the diversity of tumor and immune-associated aberrant proteomes by controlling alternative splicing and translation. They can also promote cancer-associated gene expression by regulating transcription factors, binding to DNA directly, or promoting chromatin remodeling. HnRNP are emerging as newly recognized mRNA readers. Here, we review the roles of hnRNP as regulators of the cancer-immune landscape. Dissecting the molecular functions of hnRNP will provide a better understanding of cancer-immune biology and will impact the development of new approaches to control and treat cancer.
癌症仍然是第二大死亡原因，约占所有死亡人数的 20%。不断进化的癌细胞和失调的免疫系统会产生复杂的肿瘤微环境，从而促进肿瘤的生长、转移和耐药性。在过去的几十年中，人们在破解癌细胞行为和认识免疫系统是肿瘤发生的标志方面取得了重大进展。然而，控制不断变化的癌免疫景观的潜在机制在很大程度上仍未得到探索。异质核核糖核蛋白（hnRNP）是一类高度保守的 RNA 结合蛋白家族，在包括转录、转录后修饰和翻译在内的关键细胞过程中发挥着重要作用。hnRNP 的失调是癌症发展和耐药性的关键因素。hnRNP 通过控制选择性剪接和翻译，为肿瘤和免疫相关异常蛋白质组的多样性做出贡献。它们还可以通过调节转录因子、直接与 DNA 结合或促进染色质重塑来促进与癌症相关的基因表达。hnRNP 正在成为新发现的 mRNA 读取器。在这里，我们回顾了 hnRNP 作为癌症免疫景观调节剂的作用。剖析 hnRNP 的分子功能将有助于更好地理解癌症免疫生物学，并将影响控制和治疗癌症的新方法的发展。
