Background. Exosomes can encapsulate lncRNA to mediate intercellular communication in cancer progression. Our study devoted to research the effect that long noncoding RNA Metastasis-associated lung adenocarcinoma transcript 1 (lncRNA MALAT1) influence on cervical cancer (CC). Methods. MALAT1 and miR-370-3p levels in CC was assessed using qRT-PCR. CCK-8 assay and flow cytometry were devoted to confirm the influence on MALAT1 influencing the proliferation in cisplatin-resistant CC cells. Futher more, MALAT1, combined with miR-370-3p was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay. Results. In CC tissues, MALAT1 turned into substantially expressed, cisplatin-resistant cell lines, as well as exosomes. Cell proliferation was restrained and cisplatin-induced apoptosis was promoted by way of Knockout MALAT1. And promoted the miR-370-3p level, MALAT1 targeted miR-370-3p. Promoting effect of MALAT1 on cisplatin resistance of CC was partially reversed through miR-370-3p. In addition, STAT3 may induce up-regulation of MALAT1 expression in cisplatin-resistant CC cells. It was further confirmed that the effect of MALAT1 on cisplatin-resistant CC cells was achieved by activating PI3K/Akt pathway. Conclusion. The positive feedback loop of exosomal MALAT1/miR-370-3p/STAT3 mediates the cisplatin resistance of cervical cancer cells affecting PI3K/Akt pathway. Exosomal MALAT1 may become a promising therapeutic target for treating cervical cancer.
Background Chemotherapy is among the most common treatment methods for ovarian cancer (OC). However, chemoresistance limits the effectiveness of chemotherapy and leads to treatment failure. We herein investigate the biological effect of forkhead box D3 (FOXD3) in the chemoresistance of OC cells. Methods Expression of FOXD3, miR-335 and disheveled-associated activator of morphogenesis 1 (DAAM1) was detected in OC cells and tissues. The regulatory network of FOXD3/miR-335/DAAM1 was validated by dual-luciferase reporter and ChIP assays in vitro. After ectopic expression and depletion experiments in carboplatin/paclitaxel (CP)-resistant (A2780CP) or sensitive (A2780S) OC cells, cell viability, colony formation and apoptosis were tested by CCK-8 assay, colony formation assay and flow cytometry respectively. Effects of FOXD3 on the chemoresistance of OC cells in vivo were evaluated in OC xenografts in nude mice. Results Overexpression of FOXD3 impaired the proliferation and chemoresistance of OC cells, which was related to the promotion of the miR-335 expression. Functionally, DAAM1 was a putative target of miR-335. Silencing of DAAM1 was responsible for the inhibition of myosin II activation, consequently leading to suppressed OC cell proliferation and chemoresistance. In vivo results further showed that FOXD3 weakened the chemoresistance of OC cells to CP. Conclusion Taken together, we unveil a novel FOXD3/miR-335/DAAM1/myosin II axis that regulates the chemoresistance of OC both in vitro and in vivo.
BACKGROUND Huayan Capsules (HYCA) has adjuvant therapeutic effect to the patients with OS in China, which is based on our hospital long-term clinical practice. Network pharmacology is a theory based on systems biology that helps to reveal the underlying mechanisms of action between drugs and disease development. OBJECTIVE Osteosarcoma (OS) is the most frequent primary bone sarcomas. It is commonly found in the long bones of the limbs of the human body. The purpose of study was to explore the active ingredients, targets and mechanism of HYCA in the treatment of OS through network pharmacology and molecular docking technology. METHODS TCMSP and TCMID database were used to obtain the active ingredients and targets of HYCA. Targets related to OS were obtained by GeneCards, TTD and OMIM. The related target protein network was constructed and analyzed for Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. The compound was molecularly docked with proteins associated with OS by using AutoDock Vina. RESULTS In this study, we searched that HYCA has 239 active compounds, 1703 targets and of HYCA. Meanwhile, there was 220 intersection targets of OS and HYCA. Construction of protein-protein interactions (PPI) network analysis showed that there were 25 key targets of HYCA in the treatment of OS including TP53, AKT1, etc. GO enrichment analysis mainly including cell response to hormones and other compounds. KEGG enrichment analysis obtained 196 signaling pathways, which mainly including pathways in cancer, PI3K-Aktsignaling pathway, MAPK signaling pathway. Molecular docking showed that quercetin, kamanol and luteolin have strong binding ability with AKT1, TP53. CONCLUSIONS HYCA may treat OS by regulating the pathways in cancer, PI3K-Akt and MAPK signaling pathway. We will demonstrate the relationship among the active compounds of HYCA, TCM classification of OS and signal pathway, so as to provide a systematic TCM treatment plan for the clinical treatment of OS.
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