Characterization of long non-coding RNAs and MEF2C-AS1 identified as a novel biomarker in diffuse gastric cancer

Abstract

Previous studies proved that long noncoding RNAs (lncRNAs) play important role in human cancer. However, the knowledge of genome scale expression of lncRNAs and their potential biological function in gastric cancer is still lacking. Next generation RNA sequencing (RNA-seq) was performed on tumor tissues and matched adjacent normal tissues of six diffuse gastric cancer (DGC) patients. Then we performed a comprehensive analysis on lncRNAs and mRNA. Fifty-eight lncRNAs were upregulated and 54 lncRNAs were downregulated in diffuse gastric cancer tissue compared with adjacent tissue. The numbers of up- and downregulated mRNAs were 306 and 161, respectively. In addition, we inferred the function of lncRNAs by construction of a co-expression network for deregulated mRNAs and lncRNAs. Co-expressed genes of MEF2C-AS1 and FENDRR were enriched to RAS and TGF-beta signaling pathway. MEF2C-AS1 and FENDRR expression were re-evaluated by Real-time Quantitative PCR in 42 DGC patients' tumor and normal tissues, and other 46 DGC patents' and 21 healthy controls' plasma. Validation data showed MEF2C-AS1 and FENDRR were significantly downregulated in tumor tissues compared with normal tissues. And decreased FENDRR are associated with aggressive tumor characteristics including more advanced stage (P = .030), poor differentiation (P = .043) and lymphatic metastasis (P = .001). The expression level MEF2C-AS1 was significantly lower in DGC patients' plasma than that in healthy controls' plasma. In gastric cancer cell lines, knock-down of MEF2C-AS1 or FENDRR reduced the protein levels of FAT3, NTN1 and LYVE1 (the co-expressed genes), which were related with gastric cancer cell proliferation and invasion by previous studies. In addition, knock-down of MEF2C-AS1 or FENDRR promoted aggressive tumor behaviors in in-vitro assays. In this study, we provide a valuable resource of lncRNAs which might play important roles in the function of oncogenes or tumor suppressors affecting the development and progression of diffuse gastric cancer.

Histological and mutational profile of diffuse gastric cancer: current knowledge and future challenges

“…associated with this cancer histotype [76,78,79]. Namely, KMT2C loss was shown to promote EMT and was associated with poor overall survival.…”

<p>LncRNA FENDRR attenuates colon cancer progression by repression of SOX4 protein</p>

“…Long noncoding RNAs (lncRNAs), which range from 200 nucleotides to multiple kilobases and lack of protein-coding capacity, are shown to play important roles in diverse physiological and pathological processes, such as development, immune response, metabolism, self-renewal, chemoresistance, and tumorigenesis 3–6. Recently, the regulatory roles of FOXF1 adjacent noncoding developmental regulatory RNA (FENDRR) in human breast cancer, prostate cancer, lung cancer, and gastric cancer are demonstrated 7–9. However, the functions and molecular mechanism of FENDRR in colon cancer have not been investigated.…”

FENDRR Sponges miR-424-5p to Inhibit Cell Proliferation, Migration and Invasion in Colorectal Cancer

“…Expression and survival analysis were performed and it was found that the lncRNA FENDRR was significantly decreased in tumor tissue ( Figure 1B ), and patients with low FENDRR had a much shorter survival time than those with high expression ( Figure 1C ). It has been reported that FENDRR is greatly down-regulated in various cancer tissues, which induces the malignant progression and leads to poor prognosis of cancer 20 , 21 . Hence, FENDRR was selected as our research object.…”