<p>Paeonol Inhibits Cell Proliferation, Migration and Invasion and Induces Apoptosis in Hepatocellular Carcinoma by Regulating miR-21-5p/KLF6 Axis</p>

Abstract

Background Hepatocellular carcinoma (HCC) is one of the most common tumors with high mortality. MicroRNAs (miRNAs) were reported as crucial markers for the diagnosis of HCC. Paeonol exerted many pharmacological effects on tumor progression. This study aimed to elucidate the underlying molecular mechanism of paeonol in HCC progression. Methods Cell viability was determined by Cell Counting Kit-8 (CCK-8) assay. Cell apoptosis was examined by flow cytometry. The levels of Cyclin D1, cyclin-dependent kinase 4 (CDK4), B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) were detected by Western blot assay. Cell migration and invasion were assessed by transwell assay. The levels of matrix metalloproteinase-2 (MMP2) and matrix metalloproteinase-9 (MMP9) were measured by Western blot. The expression of miR-21-5p and kruppel-like factor 6 (KLF6) was detected by quantitative real-time PCR (qRT-PCR) or Western blot assay, respectively. Dual-luciferase reporter assay was performed to analyze the interaction between miR-21-5p and KLF6. The enrichment of miR-21-5p was determined by RNA pull-down assay. Xenograft assay was conducted to analyze tumor growth in vivo. Results The results demonstrated that cell viability of Hep3B and Huh-7 cells was inhibited, while cell apoptosis was promoted after treatment with paeonol. Transwell assay indicated that cell migration and invasion were blocked in paeonol-treated cells. Moreover, miR-21-5p expression was markedly decreased in paeonol-treated cells and its knockdown suppressed cell viability, migration and invasion, but contributed to cell apoptosis. MiR-21-5p targeted KLF6 and its silencing prominently elevated KLF6 level. Furthermore, the restoration experiment determined that miR-21-5p and KLF6 were antagonisms on cell viability, apoptosis, migration and invasion. Also, paeonol abated the decrease in KLF6 level caused by miR-21-5p up-regulation. Besides, paeonol suppressed tumor growth in vivo. Conclusion Paeonol impeded cell viability, migration and invasion and triggered apoptosis by regulating miR-21-5p/KLF6 axis in HCC cells. Xenograft assay confirmed that paeonol inhibited tumor growth through miR-21-5p/KLF6 axis in HCC in vivo.

Paeonol inhibits the progression of intracerebral haemorrhage by mediating the HOTAIR/UPF1/ACSL4 axis

“… Li et al., 2020 ; Mohammed Thangameeran et al., 2020 ), and this background indicates that ferroptosis is a key process in ICH-induced neuronal injury. A previous report showed that PAN inhibited the progression of inflammation and cancer (M. Cai et al., 2020 ; Shi et al., 2020 ; J. J. Zhang et al., 2020 ).…”

“…Our research is the first to find that PAN alleviates ferroptosis in ICH, which supplements our knowledge of the underlying mechanism of PAN in ICH. It has been reported that HOTAIR participates in inflammation and cancers (L. Cai et al., 2020 ; Takei et al., 2020 ). In addition, it has been reported that HOTAIR is involved in ischaemic infarct ( Yang and Lu, 2016 ).…”

“…Paeonol (PAN, 2′-hydroxy-4′-methoxyacetophenone) is a natural product that is isolated from the genus Paeonia ( Morsy et al., 2020 ). In addition, it has been reported to have an inhibitory effect on the progression of multiple diseases (e.g., hypertension, epilepsy and arthritis) (M. Cai et al., 2020 ; Shi et al., 2020 ; Yu et al., 2020 ). Moreover, it has been previously reported that PAN increased the activity of SOD and decreased the level of MDA in ICH mice ( Li et al., 2018 ).…”

Identification of microRNA-Associated-ceRNA Networks Regulating Crop Milk Production in Pigeon (Columba livia)

“…MiR-146b-5p played a regulatory role in the proliferation and differentiation of human fibroblasts and chicken myoblasts [ 46 , 47 ]. MiR-21-5p is up-regulated in a variety of cancer cells such as non-small cell lung cancer, Hepatocellular carcinoma, melanoma, and colon adenocarcinoma cells, and has been shown to promote cell proliferation [ 48 , 49 , 50 , 51 ]. MiR-193-5p downregulation has significant angiogenic effect by inducing migration and proliferation in myocardial microvascular endothelial cells.…”

A miR-212-3p/SLC6A1 Regulatory Sub-Network for the Prognosis of Hepatocellular Carcinoma

“… 19 Zhou et al explored target SOX6 repressed proliferation of HCC cells by regulating miR-21-5p through an analysis of the effect of curcumin in HCC. 20 miR-195-5p/CDK1, miR-5589-3p/CCNB1 and let-7c-3p/CKS2 were screened as significant miRNA-mRNA axes, suggesting unfavorable prognosis in HCC. 21 The progression of HCC is caused by abnormalities in genes and biological signaling pathways.…”