Non-small cell lung cancer (NSCLC) is the most common form of cancer, resulting in cancer-related deaths worldwide. Exosomes, a subclass of extracellular vesicles, are produced and secreted from various types of cells, including cancer cells. Cancer-derived exosomes can deliver nucleic acids, proteins, and lipids to provide a favorable microenvironment that supports tumor growth through enhancing cell proliferation and metastasis. Our results showed that miR-224-5p was upregulated in NSCLC patient tissues and cell lines, with a tumor-promoting phenotype. Meanwhile, exosome-derived miR-224-5p induced cell proliferation and metastasis in NSCLC and human lung cells. Moreover, we characterized the androgen receptor (AR) as a direct target of miR-224-5p. Tumor xenograft assay experiments revealed that overexpression of miR-224-5p drove NSCLC tumor growth via the suppression of AR and the mediation of epithelial-mesenchymal transition (EMT). Collectively, our results suggest that miR-224-5p-enriched exosomes promote tumorigenesis by directly targeting AR in NSCLC, which may provide novel potential therapeutic and preventive targets for NSCLC.

Cystic kidney disease is the progressive development of multiple fluid-filled cysts that may severely compromise kidney functions and lead to renal failure. TNS1 (tensin-1) knockout mice develop cystic kidneys and die from renal failure. Here, we have established TNS1-knockout MDCK cells and applied 3D culture system to investigate the mechanism leading to cyst formation. Unlike wild-type MDCK cells, which form cysts with a single lumen, TNS1-knockout cysts contain multiple lumens and upregulated Mek/Erk activities. The multiple lumen phenotype and Mek/Erk hyperactivities are rescued by re-expression of wild-type TNS1 but not the TNS1 mutant lacking a fragment essential for its cell–cell junction localization. Furthermore, Mek inhibitor treatments restore the multiple lumens back to single lumen cysts. Mek/Erk hyperactivities are also detected in TNS1-knockout mouse kidneys. Treatment with the Mek inhibitor trametinib significantly reduces the levels of interstitial infiltrates, fibrosis and dilated tubules in TNS1-knockout kidneys. These studies establish a critical role of subcellular localization of TNS1 in suppressing Mek/Erk signaling and maintaining lumenogenesis, and provide potential therapeutic strategies by targeting the Mek/Erk pathway for cystic kidney diseases.

Plant-derived bioactive compounds, often called phytochemicals, are active substances extracted from different plants. These bioactive compounds can release therapeutic potential abilities via reducing antitumor drugs side effects or directly killing cancer cells, and others also can adjust cancer initiation and progression via regulating microRNAs (miRNAs) expression, and miRNA can regulate protein-coding expression by restraining translation or degrading target mRNA. A mass of research showed that plant-derived bioactive compounds including tanshinones, astragaloside IV, berberine, ginsenosides and matrine can inhibit tumor growth and metastasis by rescuing aberrant miRNAs expression, which has influence on tumor progression, microenvironment and drug resistance in multifarious cancers. This review aims to provide a novel understanding of plant-derived bioactive compounds targeting miRNAs and shed light on their future clinical applications.

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Lung cancer is the most deadly malignancy in the last decade, accounting for about 1.6 million deaths every year globally. Tanshinone is the constituent of Salvia miltiorrhiza; it has been found that they influence tumorigenesis. However, the role of tanshinones on lung cancer is still not clear. Let-7a-5p, a short non-coding RNA, is regarded as a suppressor gene in tumorigenesis. Herein, we verified that let-7a-5p is significantly downregulated in non-small-cell lung cancer (NSCLC) tissues and cell lines. Tanshinone suppressed the expression of aurora kinase A (AURKA), inhibited cell proliferation, and arrested cell cycle progression. Our results showed that tanshinones suppressed NSCLC by upregulating the expressions of let-7a-5p via directly targeting AURKA. Besides, the data reveal that the knockdown of AURKA can also inhibit cell proliferation, arrest cell cycle, and promote cell apoptosis. Furthermore, this study demonstrates that AURKA was negatively correlated with let-7a-5p in NSCLC patient tissues. Taken together, our findings suggest that tanshinone inhibits NSCLC by downregulating AURKA through let-7a-5p. Tanshinones and let-7a-5p have the potential to be candidates for drug development of NSCLC. In conclusion, this study revealed that tanshinones with miRNA linking lead to partial mechanism in NSCLC.