Propofol suppresses the progression of non‑small cell lung cancer via downregulation of the miR‑21‑5p/MAPK10 axis

Abstract

Non-small cell lung cancer (NSCLC) accounts for >80% of lung cancer cases and is the leading cause of cancer-associated mortality worldwide. Propofol is an anesthetic drug frequently used during tumor resection. It is also known to exert inhibitory effects on cancer. Although the role of propofol in NSCLC has been reported, its underlying mechanisms remain unknown. The present study aimed therefore to investigate the mechanisms of propofol action on NSCLC. Starbase V3.0 project was used to analyze the expression levels of microRNA-21-5p (miR-21-5p) and mitogen-activated protein kinase 10 (MAPK10) in NSCLC and adjacent normal tissues from patients with NSCLC and the association between miR-21-5p and MAPK10 expression level in NSCLC tissues. The correlation between MAPK10 expression and disease-free survival (DFS) in patients with NSCLC was analyzed using GEPIA software version 1.0. miR-21-5p and MAPK10 expression in tumor and adjacent normal tissues from patients with NSCLC was evaluated by reverse transcription-quantitative (RT-q) PCR and western blotting. Cell viability and apoptosis were assessed by using Cell Counting Kit-8 assay and flow cytometry, respectively. The interaction between miR-21-5p and MAPK10 was predicted by TargetScan/miRanda and verified by dual luciferase assay. The regulatory effect of propofol on miR-21-5p and MAPK10 expression in NSCLC cell lines was examined by RT-qPCR and western blotting. Starbase V3.0 project and the results of the present study indicated that tumor tissues presented a significantly lower MAPK10 level and a higher miR-21-5p level compared with the normal samples, and that miR-21-5p expression was negatively correlated with MAPK10 expression in the tumor tissues of patients with NSCLC. Furthermore, miR-21-5p targeted the 3'-untranslated region of MAPK10. In addition, compared with BEAS-2B cells, a higher miR-21-5p and a lower MAPK10 expression was observed in the NSCLC cell lines A549 and H1299, which was reversed by propofol. The overexpression of miR-21-5p abrogated the effects of propofol on A549 and H1299 cell viability and apoptosis by targeting MAPK10. Taken together, these findings demonstrated that propofol inhibited the viability and promoted the apoptosis of NSCLC cells by downregulating the miR-21-5p/MAPK10 axis.

Propofol induces ferroptosis and inhibits malignant phenotypes of gastric cancer cells by regulating miR-125b-5p/STAT3 axis

“…Propofol has presented significant anticancer functions in several models. It has been reported that propofol inhibits the development of nonsmall cell lung cancer by downregulating the miR215p/MAPK10 axis[ 24 ]. Propofol represses malignant progression of pancreatic cancer cells by reducing NMDA receptor[ 25 ].…”

Propofol suppresses lung cancer tumorigenesis by modulating the circ‐ERBB2/miR‐7‐5p/FOXM1 axis

“…Additionally, some references have confirmed that propofol is implicated in lung cancer development. For instance, propofol has been reported to alleviate cell viability and facilitate cell apoptosis in NSCLC by inhibiting miR‐21‐5p and elevating MAPK10 21 . Liu et al discovered that propofol restrained lung cancer cell growth and metastasis via activating miR‐1284 22 .…”

Establishment of a Novel Prognostic Prediction Model for Gastric Cancer Based on Necroptosis-Related Genes

“…MAPK10, a member of the MAPK family, plays a key role in cancer initiation and progression by acting as an integration point for multiple biochemical signals [21,22]. There is increasing evidence that it acts as a microRNA target to play a tumor-promoting or tumorsuppressing role [23][24][25]. Gao et al [26] revealed that miR-335-5p suppressed GC progression by targeting MAPK10.…”