Long non-coding RNA PXN-AS1 suppresses pancreatic cancer progression by acting as a competing endogenous RNA of miR-3064 to upregulate PIP4K2B expression

Abstract

Background Dysregulation of microRNAs (miRNAs) play critical roles in cancerous processes. Although miR-3064 was reported to be an important tumor suppressor in ovarian cancer, the cellular impact of miR-3064 on pancreatic cancer (PC) progression, its downstream target genes and upstream mechanisms that control the expression of miR-3064 remain to be fully clarified. Methods We compared miRNA expression profiles between PC tissues compared with normal tissues using a miRNA microarray analysis of clinical samples, and screened the identified miRNAs for their influence on cell proliferation. We measured the expression of miR-3064 in PC tissues and PC cell lines using quantitative real-time PCR assays. Gain- and loss-of-function experiments were conducted to explore the biologic significance of miR-3064 in PC progression both in vitro and in vivo. The interactions between miR-3064 and long noncoding RNA (lncRNA) PXN-AS1 was verified using the luciferase reporter assay and RNA immunoprecipitation assay. Results We showed that miR-3064 was significantly overexpressed in PC tissues compared to normal tissues. High miR-3064 was associated with worse prognosis in patients with PC. Functionally, ectopic expression of miR-3064 promoted the proliferation, invasion, clone formation and sphere formation of PC cells in vitro and stimulated PC growth in vivo, while specific knockdown of miR-3064 or CRISPR/Cas9-mediated knockout of miR-3064 resulted in opposite phenotypes. Further investigation revealed that miR-3064 directly targeted PIP4K2B, which was reduced in PC tissues and attenuated PC cell proliferation, invasion and sphere formation induced by miR-3064. Importantly, lncRNA PXN-AS1 expression was downregulated in PC samples, and it directly interacted with miR-3064 and suppressed its levels in PC cells. Enforced expression of PXN-AS1 remarkably decreased cell proliferation, invasion and sphere formation, while re-expression of miR-3064 abrogated these effects of PXN-AS1. Conclusions MiR-3064, a key oncogenic miRNA, could promote PC cell growth, invasion and sphere formation via downregulating the levels of tumor suppressor PIP4K2B. PXN-AS1 functioned as a sponge to suppress the expression of miR-3064. These observations offer fresh insight into the mechanisms through which miR-3064 modulates the development of PC. Electronic supplementary material The online version of this article (10.1186/s13046-019-1379-5) contains supplementary material, which is available to authorized users.

<p>LncRNA-ATB Promotes the Tumorigenesis of Ovarian Cancer via Targeting miR-204-3p</p>

“…Recent studies have indicated that lncRNAs played a key role in the progression of ovarian cancer. 16,17 In the present research, we confirmed that the expression of lncRNA-ATB was significantly upregulated in ovarian cancer cells. Li et al found that the expression of lncRNA GAS5 was notably inhibited in ovarian cancer cells.…”

<p>Downregulation of miR-486-5p Enhances the Anti-Tumor Effect of 5-Fluorouracil on Pancreatic Cancer Cells</p>

“…Pancreatic cancer is one of the most aggressive malignancies worldwide, and the treatment of pancreatic cancer is extremely difficult. 19 Evidence has illustrated that miRNAs act as novel therapeutic targets in cancer, and differential miRNA expression exhibits a functional role in the progression of pancreatic cancer. 20,21 A previous study showed that miR-486 function as an oncogenic miRNA in pancreatic cancer, suggesting that miR-486 might serve as a biomarker in patients with pancreatic cancer.…”

Long noncoding RNA LINC00514 accelerates pancreatic cancer progression by acting as a ceRNA of miR-28-5p to upregulate Rap1b expression

“…There has been considerable progress in the study of ceRNAs in PC. For example, lncRNA-PVT1 promotes PC cell proliferation and migration by sponging miR-448 [24]; cucurbitacin B inhibits PC cell proliferation both in vitro and in vivo through lncRNA-AFAP1-AS1 binding with miR-146b-5p [25]; and PXN-AS1 acts as a ceRNA of miR-3064, which upregulates PIP4K2B expression and suppresses the progression of pancreatic cancer [26]. In our research, subcellular fractionation assays indicated that LINC00514 was mostly located in the cytoplasm, which provided a basis for LINC00514 to act as a ceRNA in the initiation and progression of PC.…”