LncRNA LUCRC Regulates Colorectal Cancer Cell Growth and Tumorigenesis by Targeting Endoplasmic Reticulum Stress Response.

Guo-Hui Tang,Jia-Bian Lian,Xiu-Sheng He,Wen Liu,Lu Xia,Xiao-Ting Lin,Feng Ye,Jun Du,Xue Chen,Jian-Cheng Ding

doi:10.3389/fgene.2019.01409

Abstract

Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide, and is well known for its strong invasiveness, rapid recurrence, and poor prognosis. Long non-coding RNAs (lncRNAs) have been shown to be involved in the development of various types of cancers, including colorectal cancer. Here, through transcriptomic analysis and functional screening, we reported that lncRNA LUCRC (LncRNA Upregulated in Colorectal Cancer) is highly expressed in colorectal tumor samples and is required for colorectal cancer cell proliferation, migration, and invasion in cultured cells and tumorigenesis in xenografts. LUCRC was found to regulate target gene expression of unfolded protein response (UPR) in endoplasmic reticulum (ER), such as BIP. The clinical significance of LUCRC is underscored by the specific presence of LUCRC in blood plasma of patients with colorectal cancers. These findings revealed a critical regulator of colorectal cancer development, which might serve as a therapeutic target in colorectal cancer.

Highlights

Colorectal cancer (CRC) is one of the most common digestive tract malignancies
To identify genes that are dysregulated in colorectal cancer, RNA-seq analysis was performed for colorectal tumor tissues and the corresponding adjacent normal tissues collected from four patients with colorectal cancer
Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that genes with implications in ribosome biogenesis, cell cycle, DNA replication, immuno-response, and others were dysregulated in tumor samples (Figures S1A–D)

Summary

Introduction

Colorectal cancer (CRC) is one of the most common digestive tract malignancies. Based on the statistics from International Agency for Research on Cancer in 2018, the morbidity of colorectal cancer ranked the third and mortality the second among all cancer types (Bray et al, 2018). About 70% of patients with colorectal cancer have an average age of over 50 years old, and environmental factors were considered to play a major role in these patients. Despite continuous improvement in treatment, the survival rate of patients with advanced colorectal cancer is still not optimistic. According to SEER (Surveillance, Epidemiology, and End Results Program) statistics, the 5-year survival rate of patients with stage IV colorectal cancer is only 5% (Recio-Boiles et al, 2019a; Recio-Boiles et al, 2019b). One of the main reasons for poor prognosis is the occultation of colorectal cancer and most patients are diagnosed at the advanced stage and died due to postoperative recurrence or metastasis. Finding more effective early diagnostic markers or therapeutic targets is of great significance for improving the early diagnosis rate and improving the survival rate of colorectal cancer (Reimers et al, 2013)

Methods

Results

Conclusion