Dexmedetomidine inhibits the growth and metastasis of esophageal cancer cells by down‐regulation of lncRNA MALAT1

Abstract

This study aims to evaluate the effect of dexmedetomidine (DEX)—on esophageal cancer (EC) via regulating long noncoding RNA (lncRNA) metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1). The effect of DEX on MALAT1 expression and EC cell viability was detected. EC cells were divided into Blank, DEX, scrambled/MALAT1 siRNA, and DEX + control/MALAT1 groups, followed by a series of experiments including quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR), western blotting, 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyl tetrazolium bromide (MTT), Annexin V‐FITC/PI staining, wound healing, and Transwell assays. Additionally, mice were subjected to the subcutaneous injection of Eca109 cells transfected by control/MALAT1 activation lentiviral vector to construct EC models with the DEX treatment, and then the tumor volume and the expression of Ki‐67 and active caspase‐3 were determined. DEX reduced the expression of MALAT1 in EC cells in a dose‐dependent manner. DEX inhibited the viability of EC cells, but increased the cell apoptosis, which, however, was reversed by MALAT1 overexpression. Moreover, MALAT1 overexpression abolished the inhibitory effect of DEX on the epithelial–mesenchymal transition (EMT) of EC cells, with enhanced migration and invasion. Furthermore, DEX succeeded in decreasing the tumor volume with the down‐regulation of MALAT1. In comparison with the DEX group, mice in the DEX + MALAT1 group had larger tumors, with the up‐regulation of Ki‐67 and the down‐regulation of active caspase‐3. DEX can reduce the expression of MALAT1 in EC cells, thereby inhibiting the proliferation, invasion and migration, as well as EMT, and promoting the apoptosis of EC cells.

The crucial role of long non-coding RNAs in the pathogenesis, therapeutic response, and clinical implications of esophageal cancer

“…For instance, it has been reported that one lncRNA, Nuclear paraspeckle assembly transcript 1 (NEAT1), is elevated in EC and modulates miR-377/ E2F3 signaling pathway to encourage EC cell growth and invasion. By controlling the expression of genes involved in cell motility and invasion, a different lncRNA known as metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been related to the metastasis of EC (29,30).…”

“…Further investigation in this field may result in the discovery of novel diagnostic and prognostic biomarkers for esophageal cancer, which could improve patient outcomes by enabling earlier detection and more focused treatment (24). The potential benefits of these treatments for patients make this an attractive area of research that calls for additional inquiry, despite the difficulties in establishing effective lncRNAbased therapeutics for esophageal cancer (29).…”

Trial watch: dexmedetomidine in cancer therapy

“… 33 DEX regulates circular RNAs, thereby affecting the circ -0003340/miR-198/HMGA2 35 and circ0008035/miR-302a/E2F7 axes. 38 Moreover DEX reduces the expression of the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), thus reducing cellular viability in vitro and decreasing tumor growth in vivo 36 ( Figure 3 ). Taken together, these recent data argue that DEX could also mediate direct anti-tumor effects through a variety of mechanisms including epigenetic modifications, the induction of apoptotic and ferroptotic cell death, 42 a decrease in tumor cell migration via the expression of E-cadherin and the depletion of vimentin, and an arrest in cell cycle through the cessation of cyclin D1 synthesis.…”