Non-small cell lung cancer (NSCLC) accounts for more than 85% of lung cancer, with high morbidity and mortality. Studies have shown that microRNA can specifically inhibit the progression of NSCLC. MiR-224-5p can regulate tumor progression in many cancers, but its function and mechanism in NSCLC aren’t clear. In this study, we found that the expression of miR-224-5p was reduced in NSCLC tissue and cells than normal lung tissue and cells. At the same time, miR-224-5p negatively regulates the proliferation and migration of NSCLC cells. Inhibition of miR-224-5p expression in A549 cells could promote cell proliferation, invasion, migration and VM formation in vitro and tumor growth and lung metastasis in vivo, while over expression of miR-224-5p in H226 cells reversed the effect. Besides, we predicted target gene and found that IL6ST is a potential target gene of miR-224-5p. The expression of miR-224-5p is negatively correlated with IL6ST and activation of JAK2/STAT3 pathway. Over expression of IL6ST reversed the effects of miR-224-5p on migration, invasion and activation of JAK2/STAT3 pathway in H226 cells. In conclusion, this study revealed that miR-224-5p can inhibit the proliferation and invasion of NSCLC by targeting inhibition of IL6ST gene transcriptional and inactivation of JAK2/STAT3 signal pathway.
Background and Purpose Hepatocellular carcinoma has high ability of
vascular invasion and metastasis. Vasculogenic mimicry (VM) is closely
related to the metastasis and recurrence of hepatocellular carcinoma
(HCC). According to previous research, Chloranthus henryi has anti-tumor
effect, but its molecular mechanism in the treatment of HCC has not yet
been stated. In our study, we aimed to investigate the effect of the
extract of Chloranthus henryi in HCC and its target and molecular
mechanism. Experimental Approach In this study, we isolated a chalcone
compound from Chloranthus henryi, compound 4, identified as flavokawain
A (FKA). We determined the anti-HCC effect of FKA by MTT and identified
the target of FKA by molecular docking and CETSA. Hepatoma cells
proliferation, migration, invasion, and VM formation were examined using
EDU, wound healing, transwell, vasculogenic mimicry, and IF. WB, RT-PCR,
and cell transfection were used to explore the mechanism of FKA on
hepatoma cells. Tissue section staining is mainly used to demonstrate
the effect of FKA on HCC in vivo. Key Results We confirmed that FKA can
directly interact with CXCL12 and HCC proliferation, migration,
invasion, and VM formation were all inhibited through reversing the EMT
progress in vitro and in vivo through the PI3K/Akt/NF-κB signaling
pathway. Additionally, by overexpressing and knocking down CXCL12, we
got the same results. Conclusion and Implications FKA attenuated
proliferation, invasion and metastatic and reversed EMT in HCC via
PI3K/Akt/HIF-1α/NF-κB/Twist1 pathway by targeting CXCL12. This study
proposed that FKA may be a candidate drug and prospective strategy for
HCC therapy.
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