Long noncoding RNA LINC00473 drives the progression of pancreatic cancer via upregulating programmed death‐ligand 1 by sponging microRNA‐195‐5p

• Published in: Journal of cellular physiology Vol. 234; no. 12; pp. 23176 - 23189
• Main Authors: Zhou, Wen‐Yang, Zhang, Ming‐Ming, Liu, Chang, Kang, Ye, Wang, Jin‐Ou, Yang, Xiang‐Hong
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.12.2019
• Subjects: Apoptosis; BAX protein; Bcl-x protein; Beta cells; Cancer; CD8 antigen; CD8+ T cells; Cell migration; Cell proliferation; Cytoplasm; Interferon; Interleukins; Ligands; LINC00473; Lymphocytes; Lymphocytes T; Lymphoma; Matrix metalloproteinase; Matrix metalloproteinases; Metalloproteinase; MicroRNAs; microRNA‐195‐5p; miRNA; Pancreatic cancer; PD-L1 protein; Pheochromocytoma cells; programmed death‐ligand 1; Ribonucleic acid; RNA; siRNA; Survival; Tumorigenesis; CD8+ T cells; LINC00473; pancreatic cancer; programmed death-ligand 1; microRNA-195-5p
• ISSN: 0021-9541; 1097-4652; 1097-4652
• DOI: 10.1002/jcp.28884

Pancreatic cancer (PC) is a great health burden to patients owing to its poor overall survival rate. Long noncoding RNAs (lncRNAs) interact with microRNAs (miRs) to participate in tumorigenesis. Therefore, we aim to uncover the role and related mechanism of LINC00473 in PC through the modulation of miR‐195‐5p and programmed death‐ligand 1 (PD‐L1). Increased LINC00473 and PD‐L1 but declined miR‐195‐5p were determined in PC tissues and cell lines, and it was found that LINC00473 mainly situated in the cytoplasm. Also, miR‐195‐5p was verified to bind with both LINC00473 and PD‐L1. Next, with the aim to examine the ability of LINC00473, miR‐195‐5p, and PD‐L1 on the PC progression, the expression of LINC00473, miR‐195‐5p and PD‐L1 were altered with mimics, inhibitors, overexpression vectors or siRNAs in PC cells and cocultured CD8+ T cells. It was demonstrated that LINC00473 sponged miR‐195‐5p to upregulate PD‐L1 expression. More important, the obtained results revealed that LINC00473 silencing or miR‐195‐5p upregulation elevated the expression of Bcl‐2 associated X protein (Bax), interferon (IFN)‐γ, and interleukin (IL)‐4 but reduced the expression of B‐cell lymphoma‐2 (Bcl‐2), matrix metalloproteinase (MMP)‐2, MMP‐9, and IL‐10, thus inducing the enhancement of the apoptosis as along with the inhibition of proliferation, invasion, and migration of the PC cells. LINC00473 silencing or miR‐195‐5p elevation activated the CD8+ T cells. Taken together, LINC00473 silencing blocked the PC progression through enhancing miR‐195‐5p‐targeted downregulation of PD‐L1. This finding offers new therapeutic options for treating this devastating disease. Taken together, LINC00473 silencing blocked the pancreatic cancer progression through enhancing miR‐195‐5p‐targeted downregulation of PD‐L1. This finding offers new therapeutic options for treating this devastating disease.