Long non‑coding RNA SLNCR1 regulates non‑small cell lung cancer migration, invasion and stemness through interactions with secretory phospholipase A2

Abstract

Long non-coding RNA (lncRNA) SRA-like non-coding RNA (SLNCR1; also known as linc00673) is a recently identified oncogenic lncRNA. The role of SLNCR1 in non-small cell lung cancer (NSCLC), a common malignancy, remains poorly understood. The present study aimed to investigate the involvement of long non-coding RNA SLNCR1 in the pathogenesis of NSCLC. Reverse transcription-quantitative PCR (RT-qPCR) and ELISA were performed to measure the levels of lncRNA SLNCR1 and secretory phospholipase A2 (sPLA2) in lung biopsies, respectively. Correlations between expression levels of lncRNA SLNCR1 and sPLA2 were analyzed by Pearson's correlation analysis. Diagnostic value of lncRNA SLNCR1 for NSCLC was evaluated by receiver operating characteristic curve analysis. lncRNA SLNCR1 small interfering (si)RNA and sPLA2 overexpression vector were transfected into NSCLC cells. Cell migration, invasion and stemness were examined by Transwell migration assay, Matrigel invasion assay and flow cytometric assay, respectively. Following transfection, expression of lncRNA SLNCR1 and sPLA2 was detected by RT-qPCR and western blotting, respectively. The results demonstrated that lncRNA SLNCR1 expression levels were upregulated in tumor tissues compared with adjacent healthy tissues of patients with NSCLC. Plasma lncRNA SLNCR1 and sPLA2 expression levels were upregulated in patients with NSCLC compared with healthy controls. Plasma lncRNA SLNCR1 and sPLA2 were positively correlated in patients with NSCLC, but not in healthy controls. lncRNA SLNCR1 siRNA silencing inhibited, whereas sPLA2 overexpression promoted cell migratory and invasive abilities and stemness. lncRNA SLNCR1 siRNA silencing led to downregulated sPLA2 expression, whereas sPLA2 overexpression did not significantly affect lncRNA SLNCR1 expression. sPLA2 overexpression attenuated the inhibitory effects of lncRNA SLNCR1 siRNA silencing on cell migration, invasion and stemness. In conclusion, lncRNA SLNCR1 may regulate cancer cell migration, invasion and stemness in NSCLC through interactions with sPLA2.

Association of LINC00673 Genetic Variants with Progression of Oral Cancer

“…To date, an increasing number of lncRNAs is documented to be causally implicated in a variety of human disorders [11], including cancer. Among them, long intergenic noncoding RNA 673 (LINC00673), also referred to as SLNCR or SLNCR1, was discovered to be differentially expressed in many tumor types and to promote cancer development and progression through distinct molecular mechanisms [12][13][14][15][16][17][18][19][20][21][22]. Specifically, in spite of being noncoding, transcripts of LINC00673 can modulate chromatin dynamics and cancercausing gene expression by serving as a modular scaffold to interact with lysine-specific demethylase 1 (LSD1) and enhancer of zeste homolog 2 (EZH2) [14,16], recruiting androgen receptor (AR) and brain-specific homeobox protein 3a (Brn3a) to facilitate the expression of metalloproteinase 9 (MMP9) [13,21], stabilizing phosphorylation of dishevelled (Dvl) to activate WNT/β-catenin signaling [15], and acting as a competing endogenous RNA (ceRNA) for miR-150-5p [17], miR-515-5p [20], and miR-1231 [12].…”

Super-Enhancer LncRNA LINC00162 Promotes Progression of Bladder Cancer

“…In recent years, increasing evidence has suggested that lncRNAs can participate in the regulation of various levels of chromosome modification, RNA transcription, and protein translation in physiological cell processes (Hon et al, 2017;Park et al, 2018;Podbevsek et al, 2018). In addition, lncRNAs can also have important effects on various stages of cell physiology (Misawa et al, 2016;Roisman et al, 2019;Xu et al, 2019). At the present time, a large amount of literature has shown that lncRNAs can regulate the development of bladder cancer in various ways.…”

A review of linc00673 as a novel lncRNA for tumor regulation

“…As a result, the areas under the curve of Linc00673 in lung cancer 13 and pancreatic cancer 17 were found to be 0.683 and 0.6093, respectively. In addition to the tumor tissues, the corresponding trend of Linc00673 expression was also detected in the peripheral blood 17 , 30 . This study report suggests that Linc00673 may be a clinically effective biomarker for early molecular diagnosis.…”

“…LSD1, another important enzyme involved in epigenetic modifications, can also assist Linc00673 in promoting tumor progression via downregulating the expression of the tumor suppressor gene NCALD 13 . In addition, the high expression level of Linc00673 is also associated with the downregulation of the expression of opioid growth factor receptor (OGFR) 27 and the upregulation of the expression of secretory phospholipase A2 (spla2) 30 , although the molecular mechanisms involved in these events remain unexplored ( Figure 2 ).…”