Pancreatic cancer (PC) is a common malignant tumor of the digestive system, posing a serious threat to the life of patients. This study aims to investigate the role of LINC00847 and the LINC00847/miR-455-3p/HDAC4 mechanism in PC progression.

Material and methods:
The RNA levels of LINC00847, miR-455-3p and HDAC4 were determined by RT-qPCR. HDAC4 protein level was assessed by western blotting. Colony formation and CCK-8 assays were employed to test the proliferation of PC cells. Transwell and scratch assays were conducted to evaluate the cell invasive and migratory abilities, respectively. The effect of LINC00847 silencing on PC cells in vivo was verified using a mouse xenograft model. The correlation among LINC00847, miR-455-3p and HDAC4 was ascertained by dual-luciferase reporter (DLR) assay and Pearson’s correlation analysis.

The result showed that LINC00847 mainly localized in the cytoplasm was upregulated in PC cells and tissues. Downregulating LINC00847 hindered migration, proliferation, and invasion of PC cells in vitro. Moreover, it also suppressed tumor growth in an in vivo xenograft model. LINC00847 was found to directly target miR-455-3p. miR-455-3p overexpression inhibited cell proliferation and invasion. In addition, HDAC4 was confirmed to be a target gene of miR-455-3p, and HDAC4 overexpression overturned the impact of LINC00847 knockdown on PC cell progression.

Our findings reveal that LINC00847 potentially plays a key role in the carcinogenesis of PC progression. This effect may be mediated via regulating the miR-455-3p/HDAC4 axis. This study provides insights into the intricate molecular mechanisms underlying PC and opens avenues for potential therapeutic interventions.

Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71: 209-49.
Strobel O, Neoptolemos J, Jäger D, Büchler MW. Optimizing the outcomes of pancreatic cancer surgery. Nat Rev Clin Oncol 2019; 16: 11-26.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin 2020; 70: 7-30.
Wright MW, Bruford EA. Naming ‘junk’: human non-protein coding RNA (ncRNA) gene nomenclature. Hum Genom 2011; 5: 90-8.
Yang M, Lu H, Liu J, Wu S, Kim P, Zhou X. lncRNAfunc: a knowledgebase of lncRNA function in human cancer. Nucleic Acids Res 2022; 50: D1295-306.
Li H, Wang X, Wen C, et al. Long noncoding RNA NORAD, a novel competing endogenous RNA, enhances the hypoxia-induced epithelial-mesenchymal transition to promote metastasis in pancreatic cancer. Mol Cancer 2017; 16: 169.
Zhu H, Shan Y, Ge K, Lu J, Kong W, Jia C. LncRNA CYTOR promotes pancreatic cancer cell proliferation and migration by sponging miR-205-5p. Pancreatology 2020; 20: 1139-48.
Zhang M, Wang R, Zhao X, Lu L, Wang T. LncRNA LINK-A regulates ROCK1 expression in early-stage pancreatic adenocarcinoma. Exp Ther Med 2020; 19: 1933-39.
Li H, Chen YK, Wan Q, et al. Long non-coding RNA LINC00847 induced by E2F1 accelerates non-small cell lung cancer progression through targeting miR-147a/IFITM1 axis. Front Med (Lausanne) 2021; 8: 663558.
Tu LR, Li W, Liu J, Song XG, Xu HW. LncRNA LINC00847 contributes to hepatocellular carcinoma progression by acting as a sponge of miR-99a to induce E2F2 expression. J Biol Regul Homeost Agents 2020; 34: 2195-203.
Si L, Yang Z, Ding L, Zhang D. Regulatory effects of lncRNAs and miRNAs on the crosstalk between autophagy and EMT in cancer: a new era for cancer treatment. J Cancer Res Clin Oncol 2022; 148: 547-64.
Sharma GG, Okada Y, Von Hoff D, Goel A. Non-coding RNA biomarkers in pancreatic ductal adenocarcinoma. Semin Cancer Biol 2021; 75: 153-68.
Liu X, Ma X, Li H, et al. LINC00472 suppresses oral squamous cell carcinoma growth by targeting miR-455-3p/ELF3 axis. Bioengineered 2022; 13: 1162-73.
Sun F, Yu Z, Wu B, Zhang H, Ruan J. LINC00319 promotes osteosarcoma progression by regulating the miR-455-3p/NFIB axis. J Gene Med 2020; 22: e3248.
Zhan T, Zhu Q, Han Z, et al. miR-455-3p functions as a tumor suppressor by restraining Wnt/-catenin signaling via TAZ in pancreatic cancer. Cancer Manag Res 2020; 12: 1483-92.
Xiong G, Liu C, Yang G, et al. Long noncoding RNA GSTM3TV2 upregulates LAT2 and OLR1 by competitively sponging let-7 to promote gemcitabine resistance in pancreatic cancer. J Hematol Oncol 2019; 12: 97.
Chen S, Chen JZ, Zhang JQ, et al. Silencing of long noncoding RNA LINC00958 prevents tumor initiation of pancreatic cancer by acting as a sponge of microRNA-330-5p to down-regulate PAX8. Cancer Lett 2019; 446: 49-61.
Xia P, Liu P, Fu Q, et al. Long noncoding RNA EPIC1 interacts with YAP1 to regulate the cell cycle and promote the growth of pancreatic cancer cells. Biochem Biophys Res Commun 2020; 522: 978-85.
Li W, Hu X, Huang X. Long intergenic non-protein coding RNA 847 promotes laryngeal squamous cell carcinoma progression through the microRNA-181a-5p/zinc finger E-box binding homeobox 2 axis. Bioengineered 2022; 13: 9987-10000.
Zhao Y, Yan M, Yun Y, et al. MicroRNA-455-3p functions as a tumor suppressor by targeting eIF4E in prostate cancer. Oncol Rep 2017; 37: 2449-58.
Zhu J, Zhou Y, Zhu S, et al. circRNA circ_102049 implicates in pancreatic ductal adenocarcinoma progression through activating CD80 by targeting miR-455-3p. Mediators Inflamm 2021; 2021: 8819990.
Wen Y, Li B, He M, Teng S, Sun Y, Wang G. circHIPK3 promotes proliferation and migration and invasion via regulation of miR 637/HDAC4 signaling in osteosarcoma cells. Oncol Rep 2021; 45: 169-79.
Jin K, Zhao W, Xie X, Pan Y, Wang K, Zhang H. MiR-520b restrains cell growth by targeting HDAC4 in lung cancer. Thorac Cancer 2018; 9: 1249-54.
Ma H, Shen L, Yang H, Gong H, Du X. Circular RNA circPSAP functions as an efficient miR-331-3p sponge to regulate proliferation, apoptosis and bortezomib sensitivity of human multiple myeloma cells by upregulating HDAC4. J Pharmacol Sci 2022; 149: 27-36.
Giaginis C, Damaskos C, Koutsounas I, et al. Histone deacetylase (HDAC)-1, -2, -4 and -6 expression in human pancreatic adenocarcinoma: associations with clinicopathological parameters, tumor proliferative capacity and patients’ survival. BMC Gastroenterol 2015; 15: 148.
Yang J, Chheda C, Lim A, et al. HDAC4 mediates smoking-induced pancreatic cancer metastasis. Pancreas 2022; 51: 190-95.
Journals System - logo
Scroll to top