LncRNA LINC00857 strengthens the malignancy behaviors of pancreatic adenocarcinoma cells by serving as a competing endogenous RNA for miR-340-5p to upregulate TGFA expression.

Tingfu Li,Hongbo Zhao,Hua Zhou,Tingting Geng,Suhwan Chang

doi:10.1371/journal.pone.0247817

Abstract

BackgroundPancreatic adenocarcinoma (PAAD) is a pancreatic disease with a high mortality rate in the world. This present research intends to identify the function of lncRNA LINC00857/miR-340-5p/Transforming growth factor alpha (TGFA) in the progression of PAAD.MethodsBioinformatics analysis was used to explore the differentially expressed lncRNA/miRNA/mRNA and analyze the relationship between lncRNA/miRNA/mRNA expression and prognosis of PAAD by enquiring TCGA, GEO and GTEX. KEGG pathway analysis and GO enrichment analysis were implemented to annotate the crucial genes regulated by LINC00857. The biological behaviors of PAAD cells were detected by CCK-8, colony formation and transwell assays. Interactive associations between LINC00857 and miR-340-5p, as well as miR-340-5p and TGFA were analyzed by dual luciferase assay.ResultsBy enquiring TCGA database, we got that LINC00857 was highly expressed in patients with PAAD and positively associated with worse prognosis in PAAD patients. Moreover, LINC00857 upregulation promoted the proliferation and clone formation abilities of PAAD cells. Afterwards, the downstream miRNA and mRNA targets of LINC00857 were picked up to construct a ceRNA network. Further study revealed that TGFA expression was positively regulated by LINC00857 and negatively regulated by miR-340-5p. Besides that, the inhibitory effect of miR-340-5p on PAAD cells growth and movement can be blocked by LINC00857 upregulation. While, the malignant behavior of PAAD cells induced by TGFA overexpression can be eliminated by LINC00857 knockdown.ConclusionsUpregulation of LINC00857 improved growth, invasion and migration abilities of PAAD cells by modulation of miR-340-5p/TGFA, affording potential targets and biomarkers for the clinical diagnosis and treatment.

Highlights

Pancreatic adenocarcinoma (PAAD), as a fatal tumor, is featured by early hematopoietic and lymphocytic hyperplasia following high local recurrence rate [1]
By enquiring TCGA database, we got that LINC00857 was highly expressed in patients with PAAD and positively associated with worse prognosis in PAAD patients
With the increase of LINC00857 expression, the total survival time of PAAD patients decreased significantly (Fig 1C, P = 0.0053), which further confirmed the importance of LINC00857 in the prognosis of PDAA patients

Summary

Introduction

Pancreatic adenocarcinoma (PAAD), as a fatal tumor, is featured by early hematopoietic and lymphocytic hyperplasia following high local recurrence rate [1]. Surgical resection is still the most effective treatment for PAAD. The above reasons lead to ineffective surgical resection and drug treatment in PAAD patients, resulting in high mortality and poor prognosis in PAAD patients. Despite advances in tumor treatment, especially in targeted therapy and immunotherapy, the mortality rate of PAAD is still basically unchanged [4]. Pancreatic adenocarcinoma (PAAD) is a pancreatic disease with a high mortality rate in the world. This present research intends to identify the function of lncRNA LINC00857/miR-3405p/Transforming growth factor alpha (TGFA) in the progression of PAAD

Methods

Results

Conclusion