Small Nuclear Ribonucleoprotein Polypeptide N Accelerates Malignant Progression and Poor Prognosis in Colorectal Cancer Transcriptionally Regulated by E2F8.

Meiling Ji,Wentao Tang,Peng Zheng,Qingyang Feng,Xinyuan Lao,Jianmin Xu,Li Ren,Tianyu Liu,Yang Lv,Aobo Zhuang

doi:10.3389/fonc.2020.561287

Abstract

Colorectal cancer is a major cause of death worldwide, and the identification of new diagnostic and prognostic biomarkers is crucial to develop new strategies to avoid colorectal cancer-related deaths. Small nuclear ribonucleoprotein polypeptide N (SNRPN) is an imprinted gene that plays an important role in various neurodevelopmental disabilities. In this study, SNRPN was highly expressed in colorectal cancer tissues and involved in the progression of this disease. Immunohistochemistry analysis of 1,310 colorectal cancer tissue samples showed that SNRPN highly expressed in cancer tissues than in adjacent tissues and was mainly localized in the nucleus. Clinical pathological factor analysis demonstrated that higher expression of SNRPN was significantly associated with larger tumor size, location of the tumor on the left-sided colon, neural invasion, and distant metastasis. Univariate and multivariate analyses showed that SNRPN expression was an independent risk factor for survival, with high expression levels indicating worse overall survival. Both in vitro and in vivo experiments confirmed that high expression of SNRPN was associated with tumor proliferation, cell cycle, and metastasis. Knocking down SNRPN blocked the cell cycle at the G2/M phase transition and promoted tumor cell apoptosis, inhibiting the progression of colorectal cancer. To explore the up-steam of SNRPN, we found by luciferase reporter assay and chromosomal immunoprecipitation assay that E2F8 was a transcriptional regulator up-steam of SNRPN in colorectal cancer. Systematic studies of SNRPN will help us discover new regulatory molecules and provide a theoretical basis for finding new molecular targets for this disease.

Highlights

Colorectal cancer (CRC) is one of three most common cancers both in the incidence and the mortality worldwide [1]
small nuclear ribonucleoprotein polypeptide N (SNRPN) is an imprinted gene for paternal expression and participates in the regulation of cell differentiation, cell proliferation, embryonic development, and mental behavior
We found that SNRPN exhibits significantly increased expression levels in CRC tissues compared to adjacent normal tissues

Summary

Introduction

Colorectal cancer (CRC) is one of three most common cancers both in the incidence and the mortality worldwide [1]. As a gene-driven cancer, uncovering the molecular cascade from adenoma to cancer has greatly promoted the understanding of CRC tumorigenesis and development. With the use of targeted drugs and surgical treatment, the prognosis of the CRC patient has SNRPN Accelerates Colorectal Cancer Progerssion largely improved. The small nuclear ribonucleoprotein polypeptide N (SNRPN) is an imprinted gene. Li et al demonstrated that the abnormal expression of SNRPN impairs neurological function through regulating the nuclear receptor subfamily, group A, member 1(Nr4a1) [4]. SNRPN is responsible for splicing the calcitonin/CGRP transcript in the brain [5], and the alternative splicing has been demonstrated due to the reduced expression levels of mature U2 snRNP. The expression of SNRPN is tissue specific, and the highest expression in adult is found in the heart and brain [6]

Methods

Results

Conclusion