Long Noncoding RNA ROR Regulates Proliferation, Invasion, and Stemness of Gastric Cancer Stem Cell

Abstract

Gastric cancer remains an incurable malignance and the second leading cause of cancer death globally. Recent progress in gastric cancer research has demonstrated the crucial roles of cancer stem cells (CSCs) in the development, metastasis, and drug resistance of this disease. Various studies have highlighted the role of long noncoding RNAs (lncRNAs) in the pathogenesis of gastric cancer. In this study, through fluorescence-activated cell sorting, we isolated gastric CSCs (GCSCs) from MKN-45 cells and demonstrated for the first time that lncRNA ROR was highly expressed in CD133 GCSCs. Overexpression of lncRNA ROR significantly increased, but knockdown of lncRNA ROR inhibited the proliferation and invasion of GCSCs. Most importantly, lncRNA ROR led to upregulation of several key stemness transcriptional factors, such as OCT4, SOX2, and NANOG, as well as CD133 GCSC. Our data demonstrated that lncRNA ROR was associated with core stemness transcriptional factors and the pluripotent state of GCSCs. These results further improved our understanding of the functional cross talking network during development of GCSCs and may provide novel target for the diagnostics and therapeutics of gastric cancer.

Long Non-Coding RNAs: Key Regulators of Epithelial-Mesenchymal Transition, Tumour Drug Resistance and Cancer Stem Cells

“…Linc-ROR appears to function as a ceRNA for miR-145 to de-repress the miR-145 targets Oct4, SOX2 and Nanog [132] while overexpression of this lncRNA can further induce EMT in breast cancer cells by acting as a ceRNA for miR-205 and preventing the degradation of ZEB2, generating cells with stem cell-like properties [133]. This lncRNA has now also been shown to regulate lncRNA key stemness transcriptional factors, such as Oct4, SOX2, and Nanog and affect the CSC population in gastric cancer [437]. …”

The Long Non-Coding RNA CRNDE Promotes Colorectal Carcinoma Progression by Competitively Binding miR-217 with TCF7L2 and Enhancing the Wnt/β-Catenin Signaling Pathway

“…More than 90% of the DNA sequence is actively transcribed, but only 2% encodes protein; thus, most transcripts are as non-coding RNAs (ncRNAs) [7, 8], some of which are involved in malignant transformation and/or cancer progression [9-12]. Based on size, non-coding RNAs are divided into two groups: small ncRNAs, such as microRNAs (miRNAs, ∼22 nucleotides), which regulate gene expression and are involved in tumorigenesis [13-20], and long non-coding RNAs (lncRNAs, greater than 200 nt).…”

“…Based on size, non-coding RNAs are divided into two groups: small ncRNAs, such as microRNAs (miRNAs, ∼22 nucleotides), which regulate gene expression and are involved in tumorigenesis [13-20], and long non-coding RNAs (lncRNAs, greater than 200 nt). LncRNAs are involved in various physiological and cellular processes such as development, growth, cell cycle progression, differentiation, inflammation, tumorigenesis, migration and invasion [9-12, 21-23]. Colorectal neoplasia differentially expressed (CRNDE) was initially identified as an lncRNA in colorectal cancer and was found to be located on chromosome 16, which is important in the proliferation, migration, and invasion of colorectal tumor cells [24-28].…”

Gastric cancer: Basic aspects

“…Experimentally, the tumor‐initiating capacity Lgr5 + cells were demonstrated upon deletion of Smad4 and PTEN, which promoted the invasive intestinal‐type cancer in a murine model, while the same deletion in Lgr5 − cells failed to do so . Novel markers have also been identified, as is the case of the long noncoding RNA (lncRNA) ROR, which has been found highly expressed in CD133 + GCSCs . lncRNA ROR upregulation upregulated stemness factors such as OCT4, SOX2, and NANOG.…”