Abstract

Ribosomal proteins (RPs) are the main components of ribosomes and participate in the self-assembly of ribosomes and protein synthesis. Recent advance has shown that RPs play important roles in the tumorigenesis and drug resistance of various cancers. However, the expression status and function of RPL34 in pancreatic cancer (PC) remains unclear. In this study, we find that RPL34 is overexpressed in PC tissues and cell lines, which is correlated with decreased methylation of its promoter. Knockdown of RPL34 effectively suppresses the proliferation, colony formation, migration and drug-resistance of PC cells, which are accompanied by cell cycle arrest at the G2 phase and induction of apoptosis. In vivo assays demonstrate that RPL34 silencing inhibits PC tumor growth and metastasis. Moreover, gene expression profiling revealed that RPL34 silencing results in alteration of the MAPK and p53 signaling pathways. Clinically, our data indicate a positive association of RPL34 expression with tumor stage and metastasis in PCs. We revealed that RPL34 acts as a potential onco-protein in PC, and RPL34 may be a promising biomarker for prognosis prediction and a potential target for the treatment of PC.

Highlights

  • Pancreatic cancer (PC) is a leading cause of cancer mortality worldwide with over 330,000 new cases and approximately the same number of deaths annually [1]

  • Strong RPL34 staining was detected in almost all pancreatic cancer (PC) specimens, while weak staining was observed in matched normal tissues (Figure 1A)

  • RPL34 mRNA levels were significantly higher in PC cells than that in normal HPDE6-C7 cells, and expression of RPL34 was highest in SW1990 and PANC-1 (Figure 1D)

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Summary

Introduction

Pancreatic cancer (PC) is a leading cause of cancer mortality worldwide with over 330,000 new cases and approximately the same number of deaths annually [1]. PC may become the second cause of cancer death due to the mortality of PC deaths is likely to further rise in the coming years in the United States (US) [2]. Over the past two decades, great advances have been made in treatments for PC, including surgical resection, chemotherapy, and radiotherapy, both individually and in combination, the prognosis for PC patients, those with advanced PC, remains very poor, with a 5-year survival rate of less than 5%. Ribosomal proteins (RPs) are components of ribosomes involved in protein translation and ribosome assembly [3], which are required for the growth and survival of all types of cells [4]. Dysregulation of RPs is associated with various pathological conditions including tumorigenesis. Phosphorylation of RPS6 attenuates DNA damage and tumor suppression in www.impactjournals.com/oncotarget

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