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Thyroid hormone receptor interactor 13 (TRIP13) is an ATPase that has been found to be overexpressed in many tumors. The aim of this study was to investigate the role of TRIP13 and its mechanism of action in lung cancer. The expression of TRIP13 was examined in lung cancer tissues and corresponding normal lung tissues by western blotting. TRIP13 was overexpressed or knocked down by transient transfection or siRNA interference in lung cancer cells, respectively. The expression of key proteins associated with the Wnt signaling pathway and epithelial-mesenchymal transition (EMT) was assessed. The interaction between TRIP13 and low-density lipoprotein receptor-related protein 6 (LRP6) was examined by co-immunoprecipitation and laser confocal immunofluorescence. Moreover, this study determined the proliferative and invasive ability of cells through colony formation, cell proliferation, and Matrigel invasion assays. The expression of TRIP13 was higher in lung cancer tissues than in normal lung tissues (p = 0.002), and this correlated with poor patient prognosis (p

Purpose Keratin 17 (KRT17) is a 48 KDa type I intermediate filament, which is mainly expressed in epithelial basal cells. KRT17 has been shown to be overexpressed in many malignant tumors and play an important role in the occurrence and development of tumors. Therefore, this study explored the role and underlying mechanism of KRT17 in non-small cell lung cancers (NSCLC). Methods KRT17 expression and its correlations with clinicopathological factors were examined in lung cancer tissues by immunohistochemistry. The prognosis value of KRT17 in NSCLCs was retrieved from The Cancer Genome Atlas (TCGA) online databases. The expression level of KRT17 was increased or decreased by KRT17 gene transfection or small RNA interference in lung cancer cells, respectively. Further, proliferation and invasiveness of lung cancer cells were determined by cell proliferation and invasion assays, respectively. Finally, expression levels of proteins related to Wnt signaling pathways and epithelial mesenchymal transition (EMT) were detected by Western blot. Results The expression level of KRT17 in NSCLCs was significantly higher than normal lung tissues. High expression of KRT17 predicted poor prognosis of patients with NSCLCs, especially lung adenocarcinomas, and was correlated with poor differentiation and lymphatic metastasis. Overexpression of KRT17 enhanced, while KRT17 knockdown inhibited, the proliferation and invasiveness of lung cancer cells. Overexpression of KRT17 up-regulated β-catenin activity and levels of Wnt target genes, such as cyclin D1, c-Myc, and MMP7. Moreover, KRT17 promoted EMT by up-regulating Vimentin, MMP-9, and Snail expression and down-regulating E-cadherin expression. Conclusion Overexpression of KRT17 is common in NSCLCs and indicates poor prognosis. Overexpression of KRT17 enhances the proliferation and invasiveness of NSCLC cells by activating the Wnt signaling pathway and EMT process. KRT17 is a potential indicator of NSCLC progression and poor survival.

DEK proto-oncogene (DEK) has been demonstrated as an oncogene and is associated with the development of many types of tumor; however, the expression and role of DEK in breast cancer remain unknown. The present study aimed to determine the role of DEK in the progression of breast cancer. The expression of DEK in 110 breast cancer tissues and 50 adjacent normal breast tissues was examined using immunohistochemistry. Furthermore, DEK expression was upregulated by DEK transfection or downregulated by DEK shRNA interference in MCF7 cells. Proliferative and invasive abilities were examined in MCF7 cells using MTT assay, colony-formation assay and transwell invasion assays. The results demonstrated that DEK expression level was significantly increased in breast cancer tissues compared with normal breast tissues. Furthermore, high DEK expression was associated with high histological grade, lymph node metastasis, advanced Tumor-Node-Metastasis stage and high Ki-67 index; however, DEK expression was not associated with the expression level of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. High DEK expression indicated poor prognosis in patients with breast cancer. DEK overexpression upregulated the protein expression of β-catenin and Wnt and increased the proliferative and invasive abilities of breast cancer cells. DEK downregulation had the opposite effect. Taken together, the results from the present study demonstrated that high expression of DEK was common in patients with breast cancer and was associated with progression of the disease and poor prognosis, and that DEK overexpression promoted the proliferative and invasive abilities of breast cancer cells.

FAM83A (family with sequence similarity 83, member A) has been found to be highly expressed in cancers. The purpose of this study was to clarify the role and mechanism of FAM83A in lung cancers. The expression of FAM83A in lung cancer cells was enhanced by gene transfection or knocked down by small interfering RNA interference. The key proteins of the Wnt signaling pathway, the Hippo signaling pathway, and epithelial-mesenchymal transition (EMT) were examined using Western blot. The proliferation and invasion of lung cancer cells were examined using cell proliferation, colony formation, and invasion assays. The expression of FAM83A in lung cancer tissues was significantly increased and was correlated with advanced tumor-node-metastasis (TNM) stage and poor prognosis. Overexpression of FAM83A enhanced the proliferation, colony formation, and invasion of lung cancer cells. Meanwhile, FAM83A overexpression increased the expression of active β-catenin and Wnt target genes and the activity of EMT. Furthermore, in FAM83A-overexpressed cells, the activity of Hippo pathway was downregulated, whereas the expression of yes-associated protein (YAP) and its downstream targets cyclin E and CTGF were upregulated. The inhibitor of the Wnt signaling pathway, XAV-939, reversed the promoting effect of FAM83A on YAP, cyclin E, and CTGF. On knocking down the expression of FAM83A, we obtained the opposite results. However, the inhibitor of GSK3β, CHIR-99021, restored the expression of YAP, cyclin E, and CTGF after FAM83A was knocked down. FAM83A is highly expressed in lung cancers and correlated with advanced TNM stage and poor prognosis. FAM83A promotes the proliferation and invasion of lung cancer cells by regulating the Wnt and Hippo signaling pathways and EMT process.

Background The transcription factor PR domain containing 16 (PRDM16) is known to play a significant role in the determination and function of brown and beige fat. However, the role of PRDM16 in tumor biology has not been well addressed. Here we investigated the impact of PRDM16 on tumor growth and metastasis in lung cancer. Methods UALCAN database, immunoblotting and immunohistochemistry analysis were used to assess PRDM16 expression in lung cancer patients. Kaplan-Meier plotter database was used to analyze the overall survival of patients with lung cancer stratified by PRDM16 expression. PRDM16 overexpression and knockdown experiments were conducted to assess the effects of PRDM16 on growth and metastasis in vitro and in vivo, and its molecular mechanism was investigated in lung adenocarcinoma cells by chromatin immunoprecipitation-sequencing (ChIP-Seq), real time-quantitative PCR (RT-qPCR), luciferase assay, xenograft models and rescue experiments. Results PRDM16 was downregulated in lung adenocarcinomas, and its expression level correlated with key pathological characteristics and prognoses of lung adenocarcinoma patients. Overexpressing PRDM16 inhibited the epithelial-to-mesenchymal transition (EMT) of cancer cells both in vivo and in vitro by repressing the transcription of Mucin-4 (MUC4), one of the regulators of EMT in lung adenocarcinomas. Furthermore, deleting the PR domain from PRDM16 increased the transcriptional repression of MUC4 by exhibiting significant differences in histone modifications on its promoter. Conclusions Our findings demonstrate a critical interplay between transcriptional and epigenetic modifications during lung adenocarcinoma progression involving EMT of cancer cells and suggest that PRDM16 is a metastasis suppressor and potential therapeutic target for lung adenocarcinomas. Electronic supplementary material The online version of this article (10.1186/s13046-019-1042-1) contains supplementary material, which is available to authorized users.

Paris polyphylla Smith is a perennial medicinal plant that is wildly distributed in China, and polyphyllin is the representative medicinal ingredient from the rhizome of this plant. To date, the mechanism of steroidal saponin biosynthesis in P. polyphylla is still unclear. In this study, comparative de novo transcriptome sequencing of the rhizomes, leaves and stems from P. polyphylla were performed with the Illumina HiSeq 2500 platform. A total of 53.71 Gb of transcriptomic data was obtained from the distinct organs, and 24,297 annotated unigenes out of 50,428 assembled unigenes were achieved by aligning with the nonredundant protein sequence database; evolutionary genealogy of genes: Nonsupervised Orthologous Groups; Pfam; Swiss-Prot; euKaryotic Orthologous Groups; Gene Ontology; Kyoto Encyclopedia of Genes and Genomes (KEGG); and the Clusters of Orthologous Groups databases, and 10,141 simple sequence repeat loci were identified based on their transcriptome profiles. KEGG pathway enrichment assigned 38, 32, and 7 unigenes to terpenoid backbone biosynthesis, steroid biosynthesis, and the sesquiterpenoid and triterpenoid biosynthesis pathway, respectively. A total of 25 unigenes that encoded 17 key enzymes were identified as being involved in steroidal saponin biosynthesis in P. polyphylla. CYP90B1 (4 unigenes) and CYP724B1 (2 unigenes) from the annotated cytochrome P450 s (36 unigenes) were inferred to play probable roles in steroidal saponin biosynthesis. The phylogenetic analysis of squalene monooxygenase and cycloartenol synthase from P. polyphylla indicated close homology with multiple monocots. Furthermore, the differentially expressed genes were identified by comparison of the transcriptome profiles of distinct organs in a pairwise fashion, and the expression patterns of the candidate unigenes that were potentially responsible for steroidal saponin biosynthesis were analyzed thoroughly and coupled with the determination of polyphyllin contents in the different organs. These findings offer abundant genetic resources and a molecular basis to further study polyphyllin biosynthesis in P. polyphylla and its closely related Paris species.

Background: Nemo-like kinase (NLK) is an evolutionarily conserved MAP kinaserelated kinase involved in the pathogenesis of several human cancers. Objective: The aim of this study was to investigate the expression and role of NLK in lung cancers, and its underlying mechanisms. Methods: We examined the expression of NLK in lung cancer tissues through western blot analysis. We enhanced or knocked down NLK expression by gene transfection or RNA interference, respectively, in lung cancer cells, and examined expression alterations of key proteins in the Wnt signaling pathway and in epithelial-mesenchymal transition (EMT). We also examined the roles of NLK in the proliferation and invasiveness of lung cancer cells by cell proliferation, colony formation, and Matrigel invasion assays. Results: NLK expression was found to be significantly higher in lung cancer tissue samples than in corresponding healthy lung tissue samples. Overexpression of NLK correlated with poor prognosis of patients with lung cancer. Overexpression of NLK upregulated β-catenin, TCF4, and Wnt target genes such as cyclin D1, c-Myc, and MMP7. N-cadherin and TWIST, the key proteins in EMT, were upregulated, while E-cadherin expression was reduced. Additionally, proliferation, colony formation, and invasion turned out to be enhanced in NLK-overexpressing cells. After NLK knockdown in lung cancer cells, we obtained the opposite results. Conclusion: NLK is overexpressed in lung cancers and indicates poor prognosis. Overexpression of NLK activates the Wnt signaling pathway and EMT and promotes the proliferation and invasiveness of lung cancer cells.

Natural products from the genus Euphorbia show attention-attracting activities, such as anticancer activity. In this article, classical isolation and structure identification were used in a study on Caper Euphorbia Seed. Subsequently, MTT and wound healing assays, flow cytometry, western blotting, Hoechst 33258 staining and fluorescence microscopy examination were applied to investigate the anticancer activity of the obtained compounds. In a result, lathyrol-3-phenyl- acetate-5,15-diacetate (deoxy Euphorbia factor L1, DEFL1) was isolated from Caper Euphorbia Seed. Moreover, the NMR signals were totally assigned. DEFL1 showed potent inhibition against lung cancer A549 cells, with an IC50 value of 17.51 ± 0.85 μM. Furthermore, DEFL1 suppressed wound healing of A549 cells in a concentration-dependent manner. Mechanically, DEFL1 induced apoptosis, with involvement of an increase of reactive oxygen species (ROS), decrease of mitochondrial membrane potential (ΔΨm), release of cytochrome c, activity raise of caspase-9 and 3. Characteristic features of apoptosis were observed by fluorescence microscopy. In summary, DEFL1 inhibited growth and induced apoptosis in lung cancer A549 cells via a mitochondrial pathway.

Sucrose synthase (SS), sucrose phosphate synthase (SPS), soluble acid invertase (SAI) and neutral invertase (NI) are the key enzymes of sucrose metabolism, which activities play key role in sugar accumulation. In the present study, sugarcane variety GT28 was used as the plant material, effects of ethephon, an ethylene releasing agent, on the key enzymes of sucrose metabolism and ethylene production in relation to sucrose accumulation in sugarcane stalk and leaves were analyzed. The plants were treated by foliar spray of 400 mg/L ethephon at late growth stage. The results showed that ethylene production in leaves was positively while that in stalk internodes was negatively correlated with the maturity of leaves and stalks. The activities of SS, SPS and NI in stalk and leaves were positively while that of NI was negatively correlated with the maturity of stalks and leaves. High concentration of ethephon significantly inhibited the ethylene production and the activities of SS, SPS and NI but increased the activity of SAI enzyme in immature leaves, while promoted the ethylene production and the activities of SS, SPS and NI in maturing and matured leaves and the activity of SAI in maturing leaves but inhibited the activity of SAI in matured leaves. The active duration of ethylene releasing and the effects of ethephon on the key enzymes in leaves lasted for about 5–10 days. The ethylene production was much lower in internodes than in leaves. High concentrations of ethephon significantly increased the ethylene production in all the three different internodes in a short time but longer for immature internode, and it significantly improved the activities of SS, SPS in all the internodes and that of NI in immature and maturing internodes, but inhibited the activity of SAI in the three internodes and that of NI in matured internode. It is suggested that high concentration of ethephon may accelerate the leaf maturity and aging of the matured leaves by increasing ethylene production which could promote the activities of SS, SPS and NI in maturing and matured leaves, and the activity of SAI in immature and maturing leaves, speeding up the sucrose synthesis in maturing and matured leaf and the sucrose transportation from leaves to immature and maturing internodes, resulting in faster sugar accumulation in immature and maturing internodes of the stalks and higher sucrose content in whole cane.