Long non-coding RNA XLOC_000647 suppresses progression of pancreatic cancer and decreases epithelial-mesenchymal transition-induced cell invasion by down-regulating NLRP3

Abstract

BackgroundLong non-coding RNAs (lncRNAs) play an important role in the development and progression of various tumors, including pancreatic cancer (PC). Recent studies have shown that lncRNAs can ‘act in cis’ to regulate the expression of its neighboring genes. Previously, we used lncRNAs microarray to identify a novel lncRNA termed XLOC_000647 that was down-regulated in PC tissues. However, the expression and function of XLOC_000647 in PC remain unclear.MethodsThe expression of XLOC_000647 and NLRP3 in PC specimens and cell lines were detected by quantitative real-time PCR. Transwell assays were used to determine migration and invasion of PC cells. Western blot was carried out for detection of epithelial-mesenchymal transition (EMT) markers in PC cells. The effect of XLOC_000647 on PC cells was assessed in vitro and in vivo. The function of NOD-like receptor family pyrin domain-containing 3 (NLRP3) in PC was investigated in vitro. In addition, the regulation of NLRP3 by XLOC_000647 in PC was examined in vitro.ResultsHere, XLOC_000647 expression was down-regulated in PC tissues and cell lines. The expression level of XLOC_000647 was significantly correlated to tumor stage, lymph node metastasis, and overall survival. Overexpression of XLOC_000647 attenuated cell proliferation, invasion, and EMT in vitro and impaired tumor growth in vivo. Further, a significantly negative correlation was observed between XLOC_000647 levels and its genomic nearby gene NLRP3 in vitro and in vivo. Moreover, XLOC_000647 decreased NLRP3 by inhibiting its promoter activity. Knockdown of NLRP3 decreased proliferation of cancer cells, invasion, and EMT in vitro. Importantly, after XLOC_000647 was overexpressed, the corresponding phenotypes of cells invasion and EMT were reversed by overexpression of NLRP3.ConclusionsTogether, these results indicate that XLOC_000647 functions as a novel tumor suppressor of lncRNA and acts as an important regulator of NLRP3, inhibiting cell proliferation, invasion, and EMT in PC.

RETRACTED: Downregulation of long noncoding RNA SNHG1 inhibits cell proliferation, metastasis, and invasion by suppressing the Notch‐1 signaling pathway in pancreatic cancer

“…5,6 Increasing evidence has pointed out that lncRNAs are deregulated in various types of cancers and influence the progression of tumors. In recent years, many studies have shown that lncRNAs play important roles in gene regulation, transport, differentiation, dosage compensation, and protein synthesis.…”

ELK1‐activated GPC3‐AS1/GPC3 axis promotes the proliferation and migration of cervical cancer cells

“…Accumulating evidence shows that lncRNA exerts oncogenic or tumor suppressive role with respect to regulating cancerous biological behaviors, such as cell proliferation, migration and EMT . Accordingly, lncRNAs are increasing being identified as crucial regulators in human tumors.…”

“…Accumulating evidence shows that lncRNA exerts oncogenic or tumor suppressive role with respect to regulating cancerous biological behaviors, such as cell proliferation, migration and EMT. [29][30][31][32][33] Accordingly, lncRNAs are increasing being identified as crucial regulators in human tumors. Among these, antisense lncRNA is emerging as a vital participant with respect to affecting various cancerous developments, [34][35][36][37][38] In the present study, five candidates (DICER1-AS1, FAM83H-AS1, GPC3-AS1, DLX6-AS1 and SOX21-AS1) were subjected to qRT-PCR.…”

Evidence and perspective for the role of the NLRP3 inflammasome signaling pathway in ischemic stroke and its therapeutic potential (Review)

“…Many NLRP3 inhibitors found to have benefits following ischemic stroke were identified as natural compounds, and further research should elucidate the relationship between molecular structure and anti-NLRP3 inflammasome function. Furthermore, several microRNAs have been demonstrated to influence the NLRP3 inflammasome pathway, including miR-22 (117), miR-132 (118), and long non-coding RNA XLOc_000647 (119). Further studies should consider the modulation of the NLRP3 inflammasome post-stroke via epigenetic approaches.…”