Submicron silica particles have cytotoxicities on hepatocellular carcinoma, non-small cell lung cancer and breast cancer by unified regulating the XLOC_001659/miR-98-5p/MAP3K2-mediated pathway.

Abstract

The cytotoxicities of silica (SiO2s) particles against cancers are still controversial. In this study, the purchased submicron silica particles (SM-SiO2s) were identified by transmission electron microscopy and energy dispersive spectrometer, and it showed potent cytotoxicities on hepatocellular carcinoma (HCC), non-small cell lung cancer (NSCLC) and breast cancer (BC), which ranked the top in the incidence among the tumor types. Through the microarray assay on long noncoding RNAs (lncRNAs) from the SM-SiO2s-treated HCC, NSCLC and BC cells, followed by Venn analysis, we found that a series of lncRNAs were significantly regulated by SM-SiO2s, among of which XLOC_001659 was mostly decreased. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay confirmed that XLOC_001659 could be decreased in all the SM-SiO2s-treated HCC, NSCLC and BC cells, coupled to inhibited cell proliferation. Further, XLOC_001659 was recognized as a miR-98-5p sponge and therefore modulates the "pro-inflammatory tumor promoter" MAP3K2 expressions. The XLOC_001659/miR-98-5p/MAP3K2 axis uniformly mediated the regulation of SM-SiO2s on proliferation of HCC, NSCLC and BC cells. Further clinical experiments demonstrated that XLOC_001659 was negatively correlated with miR-98-5p level and positively correlated with MAP3K2 level, and XLOC_001659/miR-98-5p/MAP3K2 axis was significantly associated with progressions and prognosis in HCC, NSCLC and BC patients. These results provide a new clue for the anti-tumor mechanism of SM-SiO2s and a new way for drug development by using SM-SiO2s.