LncRNA DLX6-AS1 promoted cancer cell proliferation and invasion by attenuating the endogenous function of miR-181b in pancreatic cancer

Abstract

BackgroundPancreatic cancer, one of the most aggressive malignancies, ranks the fourth cause of cancer-related death worldwide. Aberrantly expressed long non-coding RNAs (lncRNAs) functioned as oncogenes or tumor suppressors in pancreatic cancer. This study aimed to determine the expression of lncRNA DLX6 antisense RNA 1 (DLX6-AS1) in pancreatic cancer tissues and to explore the DLX6-AS1-related pathway in pancreatic cancer.Materials and methodsThe gene expression levels were determined by quantitative real-time PCR, and protein expression levels were determined by western blot assay. CCK-8 assay, colony formation assay and Transwell migration and invasion assays were used to examine cell proliferation, migration and invasion. Luciferase reporter assay was used to confirm the binding between DLX6-AS1and its potential targets. In vivo study used the mouse xenograft model to test the anti-tumor effect of DLX6-AS1 knockdown.ResultsThe high expression of DLX6-AS1 was observed in pancreatic cancer tissues, and high expression of DLX6-AS1 was positively correlated with larger tumor size, advanced TNM stage and lymph node metastasis. Knockdown of DLX6-AS1 dramatically impaired cancer cell proliferation, migration and invasion. MiR-181b was the downstream target of DLX6-AS1. Knockdown of miR-181b reversed the suppression of cell viability, migration and invasion abilities caused by DLX6-AS1 knockdown. MiR-181b was found to target Zinc finger E-box-binding homeobox 2 and to modulate epithelial-mesenchymal transition. Furthermore, DLX6-AS1 knockdown inhibited tumor growth and tumor metastasis in vivo.ConclusionCollectively, our data suggested that DLX6-AS1 promotes cancer cell proliferation and invasion by attenuating the endogenous function of miR-181b in pancreatic cancer.

DLX6-AS1/miR-204-5p/OCT1 positive feedback loop promotes tumor progression and epithelial–mesenchymal transition in gastric cancer

“…Moreover, we found that DLX6-AS1 facilitated EMT accompanying actin cytoskeletal remodeling. It is worth noting that a recent study of DLX6-AS1 in pancreatic cancer has obtained similar results [18]. The EMT has been confirmed as a key mechanism that promotes invasion and immigration by inhibiting adhesion and reinforcing cell motility [27].…”

“…By analyzing the cancer genome atlas (TCGA) database, we identified a survival-related lncRNA, DLX6-AS1, which was upregulated in GC. The lncRNA DLX6-AS1 is a 1990 bp non-coding transcript located at chromosomal band 7q21.3 that has been reported to be overexpressed in lung adenocarcinoma [12], hepatocellular cancer [13,14], renal cell cancer [15], osteosarcoma [16], glioma [17] and pancreatic cancer [18]. Nevertheless, the carcinogenesis and regulatory mechanism of DLX6-AS1 in GC remains unknown.…”

LncRNA DLX6-AS1 as a potential molecular biomarker in the clinicopathology and prognosis of various cancers: a meta-analysis

“…A total of 23 articles were identified for full review, 11 of which were excluded due to lack of necessary data or in vitro studies. Finally, the remaining 12 articles [8,9,11,[14][15][16][17][18][19][20][21][22] were included in this meta-analysis. These eligible studies were published between 2017 and 2019, and covered a total of 841 patients.…”

“…DLX6-AS1 has also been proved to serve as a ceRNA to alter the expression of target miRNAs. In pancreatic cancer, DLX6-AS1 has been found to up-regulate the expression of Zinc finger E-box-binding homeobox 2 (ZEB2) by sponging miR-181b and then promote cancer cell proliferation and invasion [9]. A study by Li et al found that DLX6-AS1 modulates gliomagenesis by competing endogenous sponging miR-197-5p to relieve E2F1 [18].…”

“…For example, Sun et al reported that high expression of DLX6-AS1 was associated with tumor size and advanced clinical stage in non-small cell lung, but no significant associations between DLX6 expression and histological grade or lymph node metastasis [8]. In pancreatic cancer, high expression of DLX6-AS1 was positively correlated with large tumor size, advanced TNM stage, and lymph node metastasis [9]. Qian et al indicated that DLX6-AS1 was overexpressed in gastric cancer tissues, it was positively associated with tumor size, lymph node involvement, and tumor staging [10].…”