Keratin 80 Promotes Migration and Invasion of Non-Small Cell Lung Cancer Cells by Regulating the TGF-ß/SMAD Pathway.

Upregulation of keratin 80 (KRT80) expression levels and carcinogenic function has been found in several types of tumors. However, its contribution and mechanism in NSCLC remain to be outlined. In this study, bioinformatic investigation from the TCGA dataset revealed that KRT80 was confirmed to be elevated in human NSCLC tissues. The results of qRT-PCR and Western blot assays disclosed that KRT80 was uplifted in NSCLC cells. Data from CCK-8 and colony formation assays exhibited that depletion of KRT80 restrained NSCLC cell proliferation. Findings from Transwell and Western blot assays illustrated that downregulation of KRT80 inhibited NSCLC cell migration, invasion, and EMT. Further mechanism exploration implied that KRT80 may be included within the regulation of EMT of NSCLC cells by affecting the TGF-ß/SMAD pathway. Moreover, depletion of KRT80 attenuated xenograft tumor growth and the expressions of KRT80, Ki-67, and TGFBR1. In conclusion, depletion of KRT80 repressed NSCLC cell proliferation, invasion, and EMT, possibly mediated by the TGF-ß/SMAD signaling pathway, indicating that KRT80 may be a potentially useful target for NSCLC.

LncRNA TP73-AS1 Exacerbates the Non-Small-Cell Lung Cancer (NSCLC) Process via Regulating miR-125a-3p-Mediated ACTN4.

Background: LncRNA TP73-AS1 has been revealed to exert a noteworthy impact on the occurrence and advancement of different cancers. In this study, we explored the function of TP73-AS1 in tumor growth, cell progression as well as the relevant molecular mechanism in non-small-cell lung cancer (NSCLC). Methods: QRT-PCR was employed to assess the expression of TP73-AS1, miR-125a-3p, and actinin alpha 4 (ACTN4) in NSCLC cells. The biological effect of TP73-AS1 on NSCLC cells was assessed by cell transfection, CCK8, and transwell experiments. We further predicted the interaction among RNAs (TP73-AS1, miR-125a-3p, and ACTN4) through bioinformatics online tools and verified via luciferase reporter, RNA immunoprecipitation, and qRT-PCR assays. Xenograft models of SPC-A1 cells were conducted to test how TP73-AS1 regulates tumorigenesis. Western blot, as well as the immunohistochemistry (IHC) assays, was utilized to measure the expression levels. Functions of TP73-AS1 in NSCLC progression through the miR-125a-3p/ACTN4 axis were investigated by rescue experiments. Results: Knockdown of TP73-AS1 suppressed the growth and simultaneously attenuated the migration and invasion ability of NSCLC SPC-A1 and A549 cells. Bioinformatics and molecular mechanism assays demonstrated that TP73-AS1 could bind to miR-125a-3p/ACTN4 and regulate their expression. Moreover, the rescued-function experiment demonstrated that suppressing miR-125a-3p or elevating ACTN4 turned around the suppression effect of sh-TP73-AS1 on NSCLC progression. TP73-AS1 inhibition could also inhibit the NSCLC tumor growth and correspondingly regulated the expression of miR-125a-3p and ACTN4 in the tumor xenograft model. Conclusion: The present study indicated that TP73-AS1 affects NSCLC progression through a new competitive RNA (ceRNA) regulatory network of miR-125a-3p/ACTN4, providing an underlying target for NSCLC treatment in the future.

Icariin modulates the sirtuin/NF­κB pathway and exerts anti­aging effects in human lung fibroblasts.

Icariin (ICA) has been used as a promising anti­aging drug; however, its underlying molecular mechanism is yet to be elucidated. The present study aimed to determine the anti­aging molecular mechanisms of ICA. D­galactose (D­gal) was used to generate a cell aging model. IMR­90 human lung fibroblasts were pretreated with different concentrations of ICA (1, 2, 4, 8 and 16 µmol/l) for 6 h and subsequently incubated with D­gal (200 mmol/l) at 37˚C for 72 h. Senescence of IMR­90 cells was assessed by senescence­associated­ß­galactosidase (SA­ß­Gal) staining assay. Cell viability, and the expression levels of p53/p21, sirtuin (SIRT) 1/6 and p50/p65 were determined via the MTT assay and western blotting respectively. The results demonstrated that D­gal notably increased the proportion of SA­ß­Gal­positive cells and decreased the viability of IMR­90 cells; however, pretreatment with ICA reversed the effects of D­gal on IMR­90 cells in a concentration­dependent manner. Furthermore, it was also demonstrated that the activation of p53/p21 and nuclear factor­κB (NF­κB) signaling, and downregulation of SIRT1/6 may be involved in IMR­90 cells, in D­gal­induced aging and ICA may effectively prevent IMR­90 cells from these changes induced by D­gal. Taken together, the results of the present study suggest that the anti­aging molecular mechanisms of ICA may be associated with the regulation of the SIRT1/NF­κB pathway.