Fentanyl Inhibits Lung Cancer Viability and Invasion via Upregulation of miR-331-3p and Repression of HDAC5

Shengkai Gong; Liang Ying; Yu'ning Fan; Zhentao Sun

doi:10.2147/OTT.S281095

Fentanyl Inhibits Lung Cancer Viability and Invasion via Upregulation of miR-331-3p and Repression of HDAC5

Onco Targets Ther. 2020 Dec 23:13:13131-13141. doi: 10.2147/OTT.S281095. eCollection 2020.

Authors

Shengkai Gong¹, Liang Ying², Yu'ning Fan¹, Zhentao Sun¹

Affiliations

¹ Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, People's Republic of China.
² Department of Anesthesiology, The Second Affiliated Hospital of Zhejiang University Medical College, Hangzhou, Zhejiang 310009, People's Republic of China.

Abstract

Purpose: Non-small cell lung cancer (NSCLC) accounts for more than 80% of lung cancer cases and remains the primary cause of cancer-related deaths worldwide. Fentanyl is a commonly utilized anesthetic during the process of tumor resection, and exhibits inhibitory effects on the progression of numerous cancer types, including pancreatic cancer, colorectal cancer and gastric cancer. However, the effects of fentanyl on the cell viability and invasion of NSCLC has not been investigated. Current study aimed to investigate the effects and the mechanisms underlying the effects of fentanyl on NSCLC.

Methods: The expression of μ-opioid receptor (MOR) was proved by flow cytometry. The expression of microRNA-331-3p (miR-331-3p) and histone deacetylase 5 (HDAC5) in NSCLC tissues and cell lines are evaluated by reverse transcription-quantitative PCR (RT-qPCR) and Western blot, respectively. Cell viability and invasion are measured by cell counting kit-8 (CCK-8) assay and transwell assay, respectively. The interaction between miR-331-3p and 3'-untranslated region (UTR) of HDAC5 is predicted by TargetScan 7.1 (http://www.targetscan.org/vert_71/), validated by dual luciferase assay, RT-qPCR and Western blot.

Results: There was lower miR-331-3p expression and higher HDAC5 expression in NSCLC cell lines A549 and CALU-1 compared with BEAS-2B, which was reversed by fentanyl administration. miR-331-3p targeted 3'-UTR of HDAC5 in NSCLC cell lines A549 and CALU-1. miR-331-3p inhibitor partially abrogated the inhibitory effects of fentanyl on NSCLC cell viability and invasion by targeting HDAC5. In addition, there was higher HDAC5 expression and lower miR-331-3p expression in tumor tissues which were isolated from patients with NSCLC compared to the adjacent normal tissues, and miR-331-3p was negatively correlated with HDAC5 in NSCLC tumor tissues.

Conclusion: Fentanyl inhibits the viability and invasion of NSCLC cells by induction of miR-331-3p and reduction of HDAC5.

Keywords: HDAC5; cell invasion; cell viability; fentanyl; miR-331-3p; non-small cell lung cancer; NSCLC.