<p>Identification and Development of Long Non‐coding RNA Associated Regulatory Network in Pancreatic Adenocarcinoma</p>

Abstract

Background and Aims: Pancreatic adenocarcinoma (PAAD) is the most lethal cancer type around the world. With the in-depth exploration of the function of long non-coding RNAs (lncRNAs), the competing endogenous RNA (ceRNA) mechanism has shown its potential to partially reveal the pathogenesis of PAAD. This study aimed to construct a lncRNA-associated ceRNA network and explore ceRNA regulatory axes with experimental and prognostic value in PAAD. Methods: First, we applied differential expression analysis in the TCGA_PAAD dataset. Then, interaction analysis and survival analysis in multiple RNA interaction databases were conducted to construct a ceRNA network. Finally, a potential regulatory axis was validated using clinical samples and cell lines by quantitative realtime PCR (qRT-PCR). Results: A ceRNA network comprising 13 lncRNAs, 96 miRNAs, and 30 mRNAs was successfully constructed. Survival analysis further narrowed this network to five lncRNAs, three miRNAs, and seven mRNAs, which were significantly associated with patients' overall survival. A potential regulatory axis CASC8-miR-129-5p-TOB1 was further experimentally validated. The expression of these genes was associated with clinicopathological factors and their expression trend was consistent with ceRNA mechanism. Specifically, knockdown of lncRNA-CASC8 led to the overexpression of miR-129-5p and down-regulation of TOB1, while overexpression of CASC8 showed opposite effects. Conclusion: This novel ceRNA regulatory network could provide new insight into the pathogenesis of PAAD. The new regulatory axis CASC8-miR-129-5p-TOB1 might serve as a potential therapeutic target for patients.

Development of epithelial-mesenchymal transition-related lncRNA signature for predicting survival and immune microenvironment in pancreatic cancerwithexperiment validation

“…The low expression of CASC8 reduces the malignant biological behavior in non-small cell lung cancer [ 26 ]. In pancreatic cancer, CASC8 is specifically expressed at a high level and associated with poor prognosis [ 27 ], which is consistent with our results. LINC01133 was first reported in 2015 to be highly expressed in lung squamous cell carcinoma and then its role in tumors has been fully explored.…”

MMP25-AS1/hsa-miR-10a-5p/SERPINE1 axis as a novel prognostic biomarker associated with immune cell infiltration in KIRC

“…A large number of studies have found that long non-coding RNAs (lncRNAs) can act as miRNA sponges to regulate target gene expression. 7 , 8 The lncRNA-miRNA-mRNA ceRNA network has been shown to play vital roles in progression and metastasis of multiple cancers, such as colorectal cancer, 9 pancreatic cancer, 10 , 11 liver cancer, as well as breast cancer. 12 , 13 , 14 Nevertheless, the pivotal lncRNA-miRNA-mRNA ceRNA networks that are significantly associated with prognosis of KIRC still need further research.…”

A novel genomic instability-derived lncRNA signature to predict prognosis and immune characteristics of pancreatic ductal adenocarcinoma

“…Besides, Zhu, W. et al. found that overexpression of lncRNA-CASC8 resulted in up-regulation of TOB1 and low expression of miR-129-5p, which were associated with an increased frequency of lymph node metastasis and a higher trend of pathological stage, respectively, thus validating the CASC8-miR-129-5p-TOB1 regulatory axis ( 58 ). These studies all suggested the association of GILncSig with EMT, which we also confirmed in the present study.…”