Paternally Expressed Gene 10, or PEG10, is a retrotransposon-derived gene, originating from genetic elements that move within a genome, similar to ancient viruses integrating into host DNA. This unique evolutionary history has shaped its functions, which are now recognized as playing roles in both healthy biological processes and various disease states.
Normal Physiological Roles of PEG10
PEG10 plays a role in healthy biological processes, particularly in the development and function of the placenta. In mice, a lack of PEG10 results in early embryonic death due to severe placental defects. It contributes to the formation of the labyrinth and spongiotrophoblast layers, essential for nutrient exchange between mother and fetus.
Beyond placental development, PEG10 is involved in cellular processes like cell growth, proliferation, and differentiation. It is expressed in various adult and embryonic tissues, including the brain, liver, spleen, kidney, and lungs. The protein exists in two main isoforms, with the longer one resulting from a “−1” translational frameshifting, a mechanism also seen in some retroviruses.
PEG10 and Disease Development
PEG10’s involvement in disease is most studied in cancer, where elevated expression is frequently observed. Overexpression is often linked to tumor progression, including increased cell proliferation, invasion, and metastasis. Research suggests that PEG10 promotes cell survival by delaying the cell cycle and inhibiting programmed cell death.
In hepatocellular carcinoma (liver cancer), high PEG10 levels are associated with poor patient survival and tumor recurrence. Similarly, in breast cancer, elevated PEG10 expression correlates with distant metastasis and unfavorable clinical outcomes, enhancing cell proliferation, migration, and invasion. PEG10 also contributes to lung cancer progression by activating enzymes that break down the extracellular matrix, facilitating tumor spread.
In prostate cancer, PEG10 expression is typically low in normal tissues but increases significantly in neuroendocrine prostate cancer, an aggressive form. This upregulation promotes the growth and invasion of these cancer cells. Studies also link PEG10 to drug resistance in cancers like bladder cancer, where increased expression in drug-resistant cells can reduce chemotherapy effectiveness.
Beyond cancer, research points to PEG10’s potential involvement in neurodegenerative conditions, specifically Amyotrophic Lateral Sclerosis (ALS). Elevated PEG10 levels have been observed in the spinal cord tissue of ALS patients, suggesting a role in disease progression. This accumulation of PEG10 in nerve tissue appears to alter cell behavior, potentially interfering with communication between brain and nerve cells.
PEG10 as a Therapeutic and Diagnostic Target
Understanding PEG10’s roles has opened avenues for its use as a biomarker and therapeutic target. Its elevated expression across cancers makes it a promising candidate for early disease detection, prognosis assessment, and treatment monitoring, as high levels correlate with advanced tumor stages and poorer outcomes.
Research explores strategies to inhibit PEG10 activity for therapeutic purposes. In cancer, silencing PEG10 expression slows tumor growth, increases programmed cell death, and reduces cancer cell invasion and metastasis. Investigations include using synthetic PEG10 siRNA to block its expression.
Targeting PEG10 may also help overcome drug resistance in cancers like breast cancer, where inhibiting PEG10 has shown promise in resensitizing cells to chemotherapy. Despite challenges in clinical translation, ongoing efforts highlight PEG10’s potential to contribute to personalized medicine and novel treatment strategies for various diseases.