Qualitative Alterations in Ribosome Biogenesis and Cancer

Introduction to Ribosome Biogenesis in Cancer Development

In human interaction, protein synthesis is the fundamental cell process and ribosomes are important effectors of this process. Ribosome biogenesis is a complex process for the production of functional ribosomes. In recent years, a series of studies have shown that ribosome biogenesis is closely related to cancer development. During tumor progression, the entire process of ribosome biogenesis and ribosome assembly is modified. That is, increased tumorigenicity is associated with profound quantitative and qualitative alterations in ribosome biogenesis and function. Current research has linked ribosome biogenesis to cancer in several ways.

Fig. 1 How qualitative alterations of ribosome biogenesis in ribosomopathies may lead to cancer.¹

Relationship Between Qualitative Alterations and Cancer

Qualitative alterations in ribosome biogenesis have emerged as an important mechanism by which altered ribosome biogenesis contributes to cancer. In inherited ribosomopathies caused by genetic mutations, these gene products affect ribosome biogenesis and ultimately produce intrinsically altered ribosomes. There are two major mechanisms between ribosomopathies and cancer. First, altered ribosomes may translate differentially specific mRNAs that ultimately increase the expression of certain oncogenes or decrease the expression of certain tumor suppressors. In X-linked dyskeratosis congenita (X-DC), mutations in the DKC1 gene result in altered expression of tumor suppressors p27 and p53. A reduction in the total amount of ribosomes available for translational purposes may also lead to specific dysregulation of protein synthesis.

Second, decreased rRNA production or lack of specific ribosomal proteins results in excess production of ribosomal proteins that induce p53 stabilization by interacting with MDM2. The p53 response activation would increase the risk of cancer occurrence and development. What’s more, the relationship between qualitative alterations of ribosome biogenesis and neoplastic transformation has been proved by the frequent occurrence of ribosome changes in human sporadic cancer. RPL5-uL18 inactivation has been found in different proportions of cancer types, such as breast cancers, melanomas, glioblastomas, and childhood T-cell Acute Lymphoblastic Leukemia (T-ALL). Mutated or less expressed RPL22 -eL22 can be observed in several solid tumors, including breast, endometrial, colorectal, gastric, and non-small cell lung cancers.

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Reference

1. Penzo, Marianna, et al. "The ribosome biogenesis - cancer connection." Cells 8.1 (2019): 55.