NAP1L5 targeting combined with MYH9 Inhibit HCC progression through PI3K/AKT/mTOR signaling pathway

Abstract

Purpose:Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide. Nucleosome assembly protein 1-like 5 (NAP1L5) is a protein-coding gene that encodes a protein similar to nucleosome assembly protein 1 (NAP1). It is a histone chaperone that plays an important role in gene transcription in organisms. However, the role of NAP1L5 in the pathogenesis of hepatocellular carcinoma remains to be elucidated.Method：We used QRT-PCR, immunohistochemistry and westernbolting to detect the expression of NAP1L5 in tissues and cell lines, and analyzed the relationship between its expression and clinicopathological features and prognosis. after up-regulating and down-regulating NAP1L5 in cell lines, we used a variety of methods to verify its regulatory effect on HCC, and verified it again in animal experiments, mass spectrometry analysis to find the possible binding protein (MYH9) and downstream signaling pathway (PI3K/AK/mTOR). And verify the relationship between them.Results: In this study, low expression of NAP1L5 was found in hepatocellular carcinoma, and the downregulation of NAP1L5 was related to shorter survival and disease-free survival. In addition, its expression is also related to the tumor size and recurrence of hepatocellular carcinoma. The overexpression and knockdown of NAP1L5 by plasmid and siRNA showed that NAP1L5 inhibited the proliferation, migration and invasion and induced apoptosis of hepatoma cells. In vivo experiments confirmed that NAP1L5 can inhibit the growth and metastasis of hepatocellular carcinoma cells. In the mechanistic study, we found that NAP1L5 affects the occurrence and development of hepatocellular carcinoma by regulating MYH9 to inhibit the PI3K/AKT/mTOR signaling pathway. Conclusion: As a functional tumor suppressor, NAP1L5 is expressed at low levels in HCC. NAP1L5 inhibits the PI3K/AKT/mTOR signaling pathway in hepatocellular carcinoma by regulating MYH9.It may be a new potential target for liver cancer treatment.