Cryptotanshinone inhibits lung cancer invasion via microRNA‑133a/matrix metalloproteinase 14 regulation

Abstract

Cryptotanshinone inhibits the proliferative and colony formation abilities of human non-small cell lung cancer cells (NSCLCs). The present study reported that signal transducer and activator of transcription 3 is not the only target of cryptotanshinone during the inhibition of human NSCLCs. It was identified that cryptotanshinone upregulates the expression levels of microRNA (miR)-30d-5p, miR-126-3p, miR-133a, miR-338-3p and miR-451a, and downregulates miR-21-5p, miR-96-5p, miR-182-5p and miR-205-5p. Among these, miR-133a was the most significantly upregulated. miR-133a targets and downregulates the expression of matrix metalloproteinase (MMP)14; however, MMP15, MMP16 and MMP24 were determined to be unaffected. This process was identified to be independent of tissue inhibitor of metalloproteinases 2. Cryptotanshinone also suppresses the invasion of human NSCLCs, which may be due to the inhibited expression of MMP14. In conclusion, cryptotanshinone may serve as a potential therapeutic agent in the treatment of lung cancer.

Emerging roles of MiR-133a in human cancers

“…Matrine was found to suppress the invasion and metastasis of NCI-H1299 cells by upregulating miR-133a, which further repressed the EGFR/Akt/MMP-9 signal pathway 51 . MiR-133a could act as a tumor-suppressor by targeting and downregulating eukaryotic translation initiation factor 4A1 (eIF4A1) 52 , matrix metallopeptidase 9 (MMP9) 53 , 54 , MMP14 55 , membrane-type 1 matrix metalloproteinase (MT1-MMP) 56 , Fascin1 (FSCN1) 57 - 59 , phosphodiesterase 7A (PDE7A) 60 , Coronin-1C (CORO1C) 61 and Sox4 62 .…”

Recent advances and future directions in anti‐tumor activity of cryptotanshinone: A mechanistic review

“…It is held that administration of CT negatively affects migration and invasion of lung cancer cells. CT elevates the expression of miR‐133a to down‐regulate MMP‐14, leading to a decrease in proliferation and metastasis of cancer cells (Wang, Zhang, Zhang, Liu, & Wang, 2019).…”

“…By upregulation of miR‐133a, CT inhibits MMP‐14 to suppress migration and invasion of lung cancer cells. Besides, via overexpression of miR‐146a‐5p, CT inhibits EGFR to induce cell cycle arrest and apoptosis in lung cancer cells (Qi et al, 2019; Wang, Zhang, Zhang, et al, 2019). These two studies demonstrate that modulation of miRs can be promising in effective lung cancer therapy by CT. Future studies should be focused on revealing effect of CT on more miRs, and also, in different cancers.…”

MicroRNA‑126: A new and promising player in lung cancer (Review)

“…For instance, cryptotanshinone is an important inhibitor of the development of lung cancer cells (86). The expression levels of miR-126 were upregulated by treatment with cryptotanshinone in A549 cells (87). In addition, one EGFL7, epidermal growth factor-like domain-containing gene 7; PI3K, phosphatidylinositol-3; AKT, protein kinase B; EMT, epithelial-mesenchymal transition; NSCLC, non-small cell lung cancer; VEGF, vascular endothelial growth factor; MRP1, resistance-associated protein 1; lncRNA-PVT1-5, long non-coding RNA-PVT1-5; SLC7A5, solute carrier family 7 (cationic amino acid transporter, y+ system), member 5; miR-126-231-Exo, miR-126 loaded into 231-Exo; PTEN, phosphatase and tensin homologue; STAT3, signal transducer and activator of transcription 3; TBMS1, tubeimoside-1; VEGF-A, vascular endothelial growth factor A; VEGFR-2, vascular endothelial growth factor receptor 2; ERK, extracellular protein kinase; CT-PRFA, computed tomography-guided percutaneous radio frequency ablation, miRNA, microRNA.…”