Abstract

Paf15, which participates in DNA repair, is overexpressed in numerous solid tumors. Blocking of Paf15 inhibits the growth of many types of cancer cells; while simultaneously enhancing cellular sensitivity to UV radiation. However, its expression and function in rectal cancer (RC) remain unknown. The current study was undertaken to assess the association of Paf15 expression with RC prognosis, as well as to explore the participation of Paf15 in the response of RC cells to irradiation. Increased Paf15 expression was observed in RC tissues and associated with pTNM stage and poor survival. In vitro, Paf15 induced increased RC cell proliferation while accelerating cell cycle progression, inhibiting cell death, and protecting against gamma radiation-induced DNA damage in RC cells. In conclusion, increased Paf15 expression is associated with increased RC proliferation, decreased patient survival, and a worse radiotherapeutic response.

Highlights

  • Paf15, is a 12-kDa proliferating cell nuclear antigen (PCNA) - associated protein that is involved in cancer development and progression [1]

  • We found that Paf15 was highly expressed in rectal cancer (RC) samples and detectable at lower levels in non-cancer rectal samples

  • Our finding of detectable Paf15 expression in non-cancer tissues may reflect a growth advantage conferred by this gene

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Summary

Introduction

Paf ( known as KIAA0101, NS5ATP9, OEACT-1, and L5), is a 12-kDa proliferating cell nuclear antigen (PCNA) - associated protein that is involved in cancer development and progression [1]. There have been several published studies measuring Paf expression in cancer patient tissues, such as lung, thyroid, hepatocellular, breast, adrenal, gastric and esophageal cancers. One study evaluated mRNA levels of Paf in circulating plasma samples from colorectal cancer patients [15]. Without matched data on protein and mRNA expression in tissues, peripheral blood mRNA levels may not reflect the disease conditions studied. The current study was performed to elucidate the clinical significance of Paf in RC patient tissue samples, to assess the relationship between Paf expression, radiation response, and prognosis

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