Chitinase 3 like-1 activates the Akt pathway, inducing NF-κB-dependent release of pro-inflammatory cytokines and promoting the proliferative ability in nasopharyngeal carcinoma cells.

BACKGROUND: Chitinase 3 like-1 (CHI3L1) has been reported to function as an oncogene in many types of cancer. However, the biological function of CHI3L1 in nasopharyngeal carcinoma (NPC) remains unknown. METHODS: Differentially expressed genes (DEGs) in NPC tissues in GSE64634 and GSE12452 were downloaded from Gene Expression Omnibus (GEO). CHI3L1, interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) mRNA expression was examined by qRT-PCR. Cell proliferation was evaluated by CCK-8 and EdU incorporation assays. Western blot analysis was used to measure the changes of CHI3L1, nuclear factor-κappaB (NF-κB), and protein kinase B (Akt) pathways. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analyses were performed using DAVID database. RESULTS: We identified 3 overlapping DEGs using Draw Venn diagram, among which CHI3L1 was chosen for the following analyses. CHI3L1 was upregulated in NPC tissues and cells. CHI3L1 silencing suppressed inflammatory response by inactivating the NF-κB pathway and inhibited cell proliferation in NPC cells. On the contrary, CHI3L1 overexpression induced inflammatory response by activating the NF-κB pathway and promoted cell proliferation in NPC cells. According to GO and KEGG analyses, CHI3L1 positive regulates Akt signaling and is enriched in the PI3K-Akt pathway. CHI3L1 knockdown inhibited the Akt pathway, and CHI3L1 overexpression activated the Akt pathway in NPC cells. Akt overexpression abolished the effects of CHI3L1 knockdown on inflammatory response, NF-κB pathway, and proliferation in NPC cells. On the contrary, Akt knockdown abolished the effects of CHI3L1 overexpression on inflammatory response, NF-κB pathway, and proliferation in NPC cells. CONCLUSION: CHI3L1 knockdown inhibited NF-κB-dependent inflammatory response and promoting proliferation in NPC cells by inactivating the Akt pathway.

Clinical importance of PLA2R1 and RASSF9 in thyroid cancer and their inhibitory roles on the Wnt/ß-catenin pathway and thyroid cancer cell malignant behaviors.

Thyroid cancer is a common malignant tumor with rising incidence worldwide. The purpose of this study was to explore key genes in thyroid cancer. The differentially expressed genes were analyzed according to GEO datasets. PLA2R1 and RASSF9 levels were confirmed by UALCAN and the Human Protein Atlas databases. The disease free survival and linear correlation were analyzed by GEPIA. ROC curve was generated according to The Cancer Genome Atlas (TCGA) database. The methylation level and immune infiltration were analyzed using GSCA platform. PLA2R1, RASSF9 and Wnt/ß-catenin-related protein levels were detected by western blotting. Cell proliferation was assessed by 5-ethynyl-2'-deoxyuridine assay. Cell invasion and migration were evaluated by Transwell assay. There were 2 common differentially expressed genes (PLA2R1 and RASSF9) in thyroid cancer from GSE104005, GSE65144 and GSE53157 datasets. Decreased PLA2R1 and RASSF9 were associated with advanced stages and lower disease free survival. PLA2R1 and RASSF9 methylation levels were enhanced in thyroid cancer samples compared with normal samples. PLA2R1 methylation level was negatively correlated to its mRNA level. PLA2R1 and RASSF9 were related to immune infiltration in thyroid cancer. PLA2R1 and RASSF9 expression was associated with radioiodine resistance, and positively correlated to expression of iodide uptake-related factors. Multiple signaling pathways were involved in the action mechanisms of PLA2R1 and RASSF9, including the Wnt/ß-catenin signaling. Overexpression of PLA2R1 and RASSF9 inhibited the activation of the Wnt/ß-catenin pathway, proliferation, invasion, and migration in thyroid cancer cells. Collectively, PLA2R1 and RASSF9 are two key genes in thyroid cancer, which have potential diagnostic, prognostic, and anti-tumor effects in thyroid cancer.

Identification of the regulatory role of the circ_0004788/miR-515-5p/FGF2 network in nasopharyngeal carcinoma development.

BACKGROUND: CircularRNAs (circRNAs) played vital roles in nasopharyngeal carcinoma (NPC). However, the impacts of circ_0004788 on the development of NPC have not been explored. METHODS: Cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) and colony formation assays were applied to determine cell proliferation. Wound healing, transwell invasion assay, tube formation assay, and flow cytometry were employed for the detection of cell migration, invasion, angiogenesis, and apoptosis, respectively. Xenograft tumor experiment was used to explore the biological role of circ_0004788 in NPC in vivo. RESULTS: Circ_0004788 and fibroblast growth factor 2 (FGF2) were significantly elevated, and microRNA-515-5p (miR-515-5p) was dramatically decreased in NPC tissues and cells. The impacts of circ_0004788 knockdown on cell progression in NPC cells were reversed by miR-515-5p inhibitor, and FGF2 overexpression could block the suppressive effect of miR-515-5p on cell progression in NPC cells. CONCLUSION: Circ_0004788 knockdown restrained the progression of NPC via the miR-515-5p/FGF2 axis.

Greatly Enhanced Faradic Capacities of 3D Porous Mn3O4/G Composites as Lithium-Ion Anodes and Supercapacitors by C-O-Mn Bonding.

Through C-O-Mn bonding, graphene nanosheets are homogeneously dispersed in porous Mn3O4 to take full advantages of porous Mn3O4 and graphene nanosheets, making the as-formed three-dimensional porous Mn3O4/reduced graphene oxide (rGO) composite exhibit good electrochemical performance. Besides, C-O-Mn bonding is demonstrated to greatly promote the Faradic reactions of the composite, resulting in the enhancement of its real capacity in supercapacitor (SC) electrodes as well as lithium-ion battery (LIB) anodes. By simply fine-tuning the content of graphene (<7 wt %), the composite with 2.8 wt % of rGO delivers a high capacitance of 315 F g-1 at 0.5 A g-1 with a high rate capability of 64.7% at 30 A g-1 and an excellent cycling stability of 105% (5 A g-1, 5000 cycles) as an SC electrode. Also, the one with 6.9 wt % rGO can present a reversible capacity of more than 1500 mAh g-1 at 0.05 A g-1 as the LIB anode, the highest value reported to date, which remains 561 mAh g-1 at 1 A g-1.

A New Succinate Derivative from Ajuga decumbens.

A new succinate derivative, ethyl (5-formylfuran-2-yl)methyl succinate (1), along with three known compounds (2-4) have been isolated from the whole plants of Ajuga decumbens Thunb. Their structures were elucidated by extensive spectroscopic (1D and 2D NMR) and HR-ESI-MS data analysis, and literature values. Compound 1 was isolated as a new succinate derivative, and compounds 2 and 3 were for the first time separated from A. decumbens.

Euphorikanin A, a Diterpenoid Lactone with a Fused 5/6/7/3 Ring System from Euphorbia kansui.

Euphorikanin A (1), an unprecedented diterpenoid lactone which possesses a novel 5/6/7/3-fused tetracyclic ring skeleton, was isolated from the roots of Euphorbia kansui. The chemical structure and absolute stereochemistry were elucidated on the basis of extensive spectroscopic methods and single-crystal X-ray diffraction analysis. Compound 1 exhibited moderate cytotoxicity against two human tumor cell lines HeLa and NCI-446. A proposed biosynthetic pathway of compound 1 is also described.

A new norsesquiterpenoid from Ligularia virgaurea.

A new eremophilane norsesquiterpenoid (1), together with a known eremophilane sesquiterpenoid (2), was isolated from the leaves of Ligularia virgaurea. The structure of 1 was elucidated by a combination of spectroscopic analysis (IR, 1D NMR, 2D NMR, and HR-ESI-MS), and its absolute configuration was determined by a single-crystal X-ray diffraction experiment (with copper radiation). The known compound 2 was identified by comparison of its physical and spectral data with those reported in the literature. Compound 1 was assayed for its cytotoxic activities against human cervical carcinoma cell (HeLa) and human small cell lung cancer cell (NCI-446) lines.

A Novel Norclerodane Diterpenoid from the Roots of Croton crassifolius.

A chemical investigation of Croton crassifolius afforded a novel norclerodane diterpenoid (1) with an unprecedented six-membered oxygen ring between C-1 and C-12, together with three known compounds. The structure of the new compound was elucidated based on spectroscopic (IR, 1D, and 2D NMR) and HR-ESI-MS techniques. This report describes the first example of a natural norclerodane with a 4H-chromene ring system.