Kaempferol inhibits colorectal cancer metastasis through circ_0000345 mediated JMJD2C/ß-catenin signalling pathway.

BACKGROUND: Recurrence and metastasis are the main causes of disease deterioration in colorectal cancer (CRC) patients, yet efficient therapeutic strategies are lacking. Natural compounds for efficient antitumour therapeutics are becoming increasingly prominent. Kaempferol, one of the main components of flavonoids in plants, displays a variety of pharmacological activities. Our preliminary experiments suggested that kaempferol could inhibit CRC metastasis and is significantly associated with the ß-catenin signalling pathway. Moreover, we also defined the regulatory roles of JMJD2C in ß-catenin signalling in our previous work. PURPOSE: This study aims to reveal the mechanism by which kaempferol inhibits CRC progression and regulates the JMJD2C/ß-catenin signalling pathway. METHODS: The migratory capabilities of CRC cells after kaempferol intervention were measured by scratch wound healing and transwell assays. Circ_0000345 knockdown CRC stable cell lines were generated by lentivirus infection. The possible mechanism of kaempferol on circ_0000345 was verified by molecular-protein docking and verification program cellular thermal shift assay (CETSA). A dual luciferase reporter gene assay was carried out for the targeting relationship among circ_0000345, miR-205-5p and JMJD2C. Fluorescence in situ hybridization (FISH) was performed to determine the expression of circ_0000345 in tumour tissues. A pulmonary metastatic model of CRC in vitro was built to assess the antimetastatic effect and mechanism of kaempferol in vivo. RESULTS: In vitro, kaempferol inhibits the ability to migrate of CRC cells by reducing the activation of the JMJD2C/ß-catenin signalling pathway. MiR-205-5p is a key bridge for kaempferol to inhibit the expression of JMJD2C. The function of miR-205-5p is impeded by circ_0000345, which shows higher expression levels in human metastatic CRC tissues than nonmetastatic CRC tissues, and its formation is regulated by the RNA-binding proteins HNRNPK and HNRNPL. Mechanistically, kaempferol physically interacts with HNRNPK and HNRNPL to suppress JMJD2C by downregulating the expression of circ_0000345. In vivo, kaempferol suppresses CRC lung metastasis. Kaempferol inhibits the activation of JMJD2C/ß-catenin signalling through reducing the expression of circ_0000345 in the CRC lung metastasis model. CONCLUSION: Circ_0000345 enhances activation of the JMJD2C/ß-catenin signalling pathway through miR-205-5p to promote CRC metastasis. Kaempferol inhibits CRC metastasis through the circ_0000345-mediated JMJD2C/ß-catenin signalling pathway, and this effect is influenced as a direct consequence of the binding of kaempferol with HNRNPK and HNRNPL. This provides promising therapeutic and/or adjuvant agents for advanced CRC and sheds light on the multifaceted role of phytomedicine in cancer.

Corrigendum to "The Chinese Medicine, Jiedu Recipe, Inhibits the Epithelial Mesenchymal Transition of Hepatocellular Carcinoma via the Regulation of Smad2/3 Dependent and Independent Pathways".

[This corrects the article DOI: 10.1155/2018/5629304.].

Construction of a high-density genetic linkage map and QTL analysis of morphological traits in an F1 Malusdomestica × Malus baccata hybrid.

Apple is considered the most commonly grown fruit crop in temperate regions that brings great economic profits to fruit growers. Dwarfing rootstocks have been extensively used in apple breeding as well as commercial orchards, but the molecular and genetic basis of scion dwarfing and other morphological traits induced by them is still unclear. At present, we report a genetic map of Malusdomestica × Malus baccata with high density. The F1 population was sequenced by a specific length amplified fragment (SLAF). In the genetic map, 5064 SLAF markers spanning 17 linkage groups (LG) were included. Dwarf-related and other phenotypic traits of the scion were evaluated over a 3-year growth period. Based on quantitative trait loci (QTL) evaluation of plant height and trunk diameter, two QTL clusters were found on LG 11, which exhibited remarkable influences on dwarfing of the scion. In this analysis, QTL DW2, which was previously reported as a locus that controls dwarfing, was confirmed. Moreover, three novel QTLs for total flower number and branching flower number were detected on LG2 and LG4, exhibited the phenotypic variation that has been explained by QTL ranging from 8.80% to 34.80%. The findings of the present study are helpful to find scion dwarfing and other phenotypes induced by rootstock in the apple. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-021-01069-0.

The Chinese Medicine, Jiedu Recipe, Inhibits the Epithelial Mesenchymal Transition of Hepatocellular Carcinoma via the Regulation of Smad2/3 Dependent and Independent Pathways.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. In China, traditional Chinese herb medicine has been widely used in the treatment of HCC. Jiedu Recipe (JR) is a common used prescription which has shown good results against HCC. However, the exact mechanisms of JR are still unknown. Therefore, we investigated the efficacy of JR on HCC in the current study. JR inhibited the cell viability of both SMMC-7721 and Huh7 cells in both time- and dose-dependent manners. Transwell assay revealed that JR decreased the number of migrated cells of SMMC-7721 cells. JR treatment increased the E-cadherin expression level and decreased the levels of p-Smad2/3 and Smad2/3. Further study showed that JR reversed the effect of TGFß1 on the expression of E-cadherin, vimentin, N-cadherin, and MMP2/9. JR also significantly inhibited TGFß1-induced migration and invasion of SMMC-7721 and Huh7 cells determined by wound healing assay and transwell assay. TGFß1 treatment increased the phosphorylation of Smad2/3, p38 MAPK, JNK, ERK1/2, and Akt in SMMC-7721 cells and pretreatment with JR blocked TGFß1-induced activation of Smad2/3 and Akt and MAPKs. In conclusion, JR inhibits liver cancer cells migration and invasion through epithelial mesenchymal transition (EMT) inhibition via Smad2/3 dependent and independent pathways, suggesting it is an effective therapeutic strategy against HCC metastasis.

[Effects of Compound Aconitum Polysaccharide on Glycosylation of Tumor Cells].

Objective To observe inducing or inhibiting effects of Chinese medicine (CM) poly- saccharides on glycoprotein chain synthetized different glycosyltransferases, thus disclosing targets of CM polysaccharides and its mechanisms. Methods In vivo anti-tumor effects of CM polysaccharides were observed using the inhibiting rate of tumor growth by dividing different Aconitum containing groups. Effects of CM polysaccharides on liver cancer cell SK-HEP-1 glycosyltransferase and tumor related gene expressions were observed. Meanwhile, changes of polylactosamine expression were detected using flow cytometry (FCM) with polylactosamine specific biotin labeling lectin. Results Compared with the model group, the average tumor weight was significantly lower in each medication group (P <0. 01). Compared with the adriamycin group, no significant difference in average tumor weight of the three compound groups (P>0. 05). The expression level of polylactosamine was reduced after adding Aconitum polysac- charide; and CM compound polysaccharides respectively. Conclusions Polysaccharide compound showed similar anti-tumor effect as that of adriamycin. Besides, polylactosamine expression level was reduced in the three compound groups along with increased prepared Aconitum polysaccharide, with more obvious anti-tumor effects shown.

Diosgenin induces G2/M cell cycle arrest and apoptosis in human hepatocellular carcinoma cells.

Diosgenin is a major compound of Dioscoreaceae plants such as yam, which is used as a drug in Traditional Chinese Medicine, and a common vegetable worldwide. The anticancer effect of diosgenin has been reported in various tumor cells, including leukemia, gastric, colorectal, and breast cancer. However, the activity of diosgenin on hepatocellular carcinoma (HCC) and the underlying mechanism have not been completely investigated. Therefore, we investigated the efficacy and associated mechanisms of diosgenin in HCC cells. Flow cytometric analysis was performed to determine the presence of cell cycle arrest and apopotic cells. Diosgenin significantly inhibited the growth of Bel-7402, SMMC-7721 and HepG2 HCC cells in a concentration-dependent manner. Diosgenin treatment for 24 h induced G2/M cell cycle arrest and apoptosis of hepatoma cells. Diosgenin inhibited Akt phosphorylation and upregulated p21 and p27 expression, but did not alter the expression of p53, suggesting diosgenin-induced upregulation of p21 and p57 is p53-independent in HCC cells. Diosgenin induced HCC cell apoptosis by activating caspase cascades -3, -8 and -9. However, diosgenin did not affect Bcl-2 and Bax levels. In conclusion, results of the present study suggest that diosgenin may be an active anti-HCC agent obtained from natural plants and provide new insights in understanding the mechanisms of diosgenin.

[Correlation between the width of lingual vein and the changes of hemodynamics of portal system in patients with primary liver cancer].

OBJECTIVE: To explore the correlation between the width of lingual varix and changes of hemodynamics of portal system in patients with primary liver cancer so as to supply the data for the forecast of portal hypertension by observing lingual varix. METHODS: The diameter of lingual vein (Dlv) was measured by vernier caliper as dependent variable, and the diameters and indexes of hemodynamics of portal vessels were measured by Doppler as independent variables, then a multipe stepwise analysis was performed. RESULTS: The diameters of portal vein (Dpv) and splenic vein (Dsv) entered the formula Dlv (mm) = 0.185 + 0.311 Dsv (mm) + 0.236 Dpv (mm) when the entry and removal values were alpha(in)=0.10 and alpha(out)=0.15, respectively. CONCLUSION: The width of lingual vein is closely correlated with the diameters of portal vein and splenic vein in patients with primary liver cancer.

[Comparative study on normal tongue manifestation in patients with primary liver cancer and healthy adults].

OBJECTIVE: To find out some microscopically visible morphological differences in normal tongue manifestation between patients with primary liver cancer and healthy adults, and provide some beneficial evidences for microcosmic syndrome differentiation of tongue inspection. METHODS: Microcirculations of the tongue tip, which represented the macroscopical normal tongue manifestation, were observed under an optical microscope in patients with primary liver cancer and healthy adults. Exfoliated cells from tongue coating were examined by hematoxylin-eosin staining. RESULTS: The proportion of normal tongue manifestation was larger in healthy adults (38.89%) than that in patients with primary liver cancer (2.32%). The total score of microcirculation of tongue tip and the maturation index of exfoliated cells from tongue coating were both higher in patients with primary liver cancer than those in healthy adults with normal tongue manifestation (P<0.01, P<0.05). CONCLUSION: Normal tongue manifestation, which is macroscopically visible, can be observed in both patients with primary liver cancer and healthy adults, but there exists obvious difference in microcosmic view.