[Identification and biological characteristics of violet root rot pathogen of Pseudostellaria heterophylla in Fujian province].

Violet root rot is one of the main root diseases in the production process of Pseudostellaria heterophylla. To clarify the pathogenic species that cause the violet root rot of P. heterophylla in Fujian province, the roots and the sclerotia with violet root rot symptoms were collected from the main producing areas of P. heterophylla(Fujian province) from 2017 to 2021, and the pathogens were isolated by tissue separation method and identified by morphology and multi-gene phylogenetic analysis. Additionally, the biological characteristics of the pathogens were studied and the fungicides were determined. The results showed that 78 strains of violet root rot were isolated from the collected root samples, which belonged to one type after preliminary morphological identification. Two represen-tative strains were selected from the pathogens for multi-gene phylogenetic analysis, and they were clustered with Helicobasidium mompa together. The suitable culture conditions for the mycelium were OA medium, 25 ℃, pH 6, and ammonium oxalate as the nitrogen source. The lethal temperature of the mycelium was 50 ℃ for 10 minutes. Moreover, 99.1% propiconazole and 98.7% azoxystrobin had the optimal bacteriostatic effect, and the concentrations with the 50% bacteriostatic rate were 16.85 and 12.24 µg·mL~(-1), respectively. On the basis of the above results, the pathogen causing violet root rot of P. heterophylla in Fujian province was H. mompa. The medium type, growth temperature, pH value, nitrogen source, etc. had significant effect on the growth of mycelium.

[Identification and biological characterization of pathogen causing black spot of Pseudostellaria heterophylla in Fujian province].

In Zherong county, Fujian province, the black spot of Pseudostellaria heterophylla often breaks out in the rainy season from April to June every year. As one of the main leaf diseases of P. heterophylla, black spot seriously affects the yield and quality of the medicinal material. To identify and characterize the pathogens causing black spot, we isolated the pathogens, identified them as a species of Alternaria according to Koch's postulates, and then tested their pathogenicity and biological characteristics. The results showed that the pathogens causing P. heterophylla black spot were A. gaisen, as evidenced by the similar colony morphology, spore characteristics, sporulation phenotype, and the same clade with A. gaisen on the phylogenetic tree(the maximum likelihood support rate of 100% and the Bayesian posterior probability of 1.00) built based on the tandem sequences of ITS, tef1, gapdh, endoPG, Alta1, OPA10-2, and KOG1077. The optimum conditions for mycelial growth of the pathogen were 25 ℃, pH 5-8, and 24 h dark culture. The lethal conditions for mycelia and spores were both treatment at 50 ℃ for 10 min. We reported for the first time the A. gaisen-caused black spot of P. heterophylla. The results could provide a theoretical basis for the diagnosis and control of P. heterophylla leaf spot diseases.

CMTM7 as a novel molecule of ATG14L-Beclin1-VPS34 complex enhances autophagy by Rab5 to regulate tumorigenicity.

BACKGROUND: CMTM7 is a tumor suppressor that positively regulates EGFR degradation by promoting Rab5 activation, and plays a vital role in tumor progression. Rab5 forms complexes with Beclin1 and VPS34, and acts in the early stage of autophagy. However, the affects of CMTM7 on autophagy and its mechanism are still unclear. METHODS: The effect of CMTM7 on autophagy induction was confirmed by western blotting, confocal microscopy and transmission electron microscopy. Co-immunoprecipitation was used to analyse the interaction of CMTM7 with autophagy initiation complex and Rab5. The xenograft model in nude mice was used to elucidate the function of CMTM7 in tumorigenicity and autophagy in vivo. RESULTS: In this study, we first demonstrated that CMTM7 facilitated the initiation of autophagosome formation, which consequently promoted the subsequent multistage process of autophagic flux, i.e. from autophagosome assembly till autolysosome formation and degradation. Confocal and co-immunoprecipitation showed that CMTM7 interacted with Rab5, VPS34, Beclin1, and ATG14L, but not with ULK1, UVRAG and LC3B. CMTM7 also increased the activity of ATG14L-linked VPS34 complex and its association with Rab5. Both in vitro and in vivo experiments demonstrated that knockdown of CMTM7 enhanced tumor growth by impairing autophagy. CONCLUSION: These findings highlighted the role of CMTM7 in the regulation of autophagy and tumorigenicity, revealing it as a novel molecule that is associated with the interaction of Rab5 and ATG14L-Beclin1-VPS34 complex. Video Abstract.

CMTM3 inhibits cell migration and invasion and correlates with favorable prognosis in gastric cancer.

The CKLF-like MARVEL transmembrane domain containing 3 (CMTM3) gene is a novel tumor suppressor with frequent epigenetic inactivation. In this study, we showed the role played by CMTM3 in gastric cancer cells as a tumor suppressor gene, and examined the correlation between CMTM3 expression and clinicopathological parameters using immunohistochemistry in gastric cancer patients with different pathological stages (n = 350). We found that CMTM3 expression was reduced or silenced by epigenetic regulation in gastric cell lines, and dramatically downregulated in primary gastric cancer tissues. Restoration of CMTM3 significantly affected migration and invasion of AGS and SGC-7901 cells (P < 0.001). In vivo experiments showed that peritoneal disseminated metastases were significantly suppressed by CMTM3 (P < 0.001). We further showed that the expression of MMP2 and the phosphorylation of Erk1/2 were decreased when CMTM3 was restored. In addition, by immunohistochemical staining, we found that the expression of CMTM3 was remarkably weaker in gastric cancer tissues than in normal mucosae (P = 0.008), and was significantly correlated with gender (P = 0.033), tumor depth (P = 0.049), stage (P = 0.021), and histological grade (P = 0.022). More importantly, CMTM3 expression was associated with prognosis in gastric cancer patients (P = 0.041), and was a significant independent prognostic indicator (hazard ratio = 0.704, 95% confidence interval, 0.498-0.994; P = 0.046). Our findings indicate that CMTM3 regulates migration and invasion of gastric cancer cells. Moreover, CMTM3 is a candidate marker for prognosis of gastric cancer in the clinic.

Whole-genome sequencing in medicinal plants: current progress and prospect.

Advancements in genomics have dramatically accelerated the research on medicinal plants, and the development of herbgenomics has promoted the "Project of 1K Medicinal Plant Genome" to decipher their genetic code. However, it is difficult to obtain their high-quality whole genomes because of the prevalence of polyploidy and/or high genomic heterozygosity. Whole genomes of 123 medicinal plants were published until September 2022. These published genome sequences were investigated in this review, covering their classification, research teams, ploidy, medicinal functions, and sequencing strategies. More than 1,000 institutes or universities around the world and 50 countries are conducting research on medicinal plant genomes. Diploid species account for a majority of sequenced medicinal plants. The whole genomes of plants in the Poaceae family are the most studied. Almost 40% of the published papers studied species with tonifying, replenishing, and heat-cleaning medicinal effects. Medicinal plants are still in the process of domestication as compared with crops, thereby resulting in unclear genetic backgrounds and the lack of pure lines, thus making their genomes more difficult to complete. In addition, there is still no clear routine framework for a medicinal plant to obtain a high-quality whole genome. Herein, a clear and complete strategy has been originally proposed for creating a high-quality whole genome of medicinal plants. Moreover, whole genome-based biological studies of medicinal plants, including breeding and biosynthesis, were reviewed. We also advocate that a research platform of model medicinal plants should be established to promote the genomics research of medicinal plants.

Application of radiomics in diagnosis and treatment of lung cancer.

Radiomics has become a research field that involves the process of converting standard nursing images into quantitative image data, which can be combined with other data sources and subsequently analyzed using traditional biostatistics or artificial intelligence (Al) methods. Due to the capture of biological and pathophysiological information by radiomics features, these quantitative radiomics features have been proven to provide fast and accurate non-invasive biomarkers for lung cancer risk prediction, diagnosis, prognosis, treatment response monitoring, and tumor biology. In this review, radiomics has been emphasized and discussed in lung cancer research, including advantages, challenges, and drawbacks.

Comparative analysis of 17 complete chloroplast genomes reveals intraspecific variation and relationships among Pseudostellaria heterophylla (Miq.) Pax populations.

Pseudostellaria heterophylla (Miq.) Pax is a well-known medicinal and ecologically important plant. Effectively distinguishing its different genetic resources is essential for its breeding. Plant chloroplast genomes can provide much more information than traditional molecular markers and provide higher-resolution genetic analyses to distinguish closely related planting materials. Here, seventeen P. heterophylla samples from Anhui, Fujian, Guizhou, Hebei, Hunan, Jiangsu, and Shandong provinces were collected, and a genome skimming strategy was employed to obtain their chloroplast genomes. The P. heterophylla chloroplast genomes ranged from 149,356 bp to 149,592 bp in length, and a total of 111 unique genes were annotated, including 77 protein-coding genes, 30 tRNA genes, and four rRNA genes. Codon usage analysis showed that leucine had the highest frequency, while UUU (encoding phenylalanine) and UGC (encoding cysteine) were identified as the most and least frequently used codons, respectively. A total of 75-84 SSRs, 16-21 short tandem repeats, and 27-32 long repeat structures were identified in these chloroplast genomes. Then, four primer pairs were revealed for identifying SSR polymorphisms. Palindromes are the dominant type, accounting for an average of 47.86% of all long repeat sequences. Gene orders were highly collinear, and IR regions were highly conserved. Genome alignment indicated that there were four intergenic regions (psaI-ycf4, ycf3-trnS, ndhC-trnV, and ndhI-ndhG) and three coding genes (ndhJ, ycf1, and rpl20) that were highly variable among different P. heterophylla samples. Moreover, 10 SNP/MNP sites with high polymorphism were selected for further study. Phylogenetic analysis showed that populations of Chinese were clustered into a monophyletic group, in which the non-flowering variety formed a separate subclade with high statistical support. In this study, the comparative analysis of complete chloroplast genomes revealed intraspecific variations in P. heterophylla and further supported the idea that chloroplast genomes could elucidate relatedness among closely related cultivation materials.

The gastrodin biosynthetic pathway in Pholidota chinensis Lindl. revealed by transcriptome and metabolome profiling.

Pholidota chinensis Lindl. is an epiphytic or lithophytic perennial herb of Orchidaceae family used as a garden flower or medicinal plant to treat high blood pressure, dizziness and headache in traditional Chinese medicine. Gastrodin (GAS) is considered as a main bioactive ingredient of this herb but the biosynthetic pathway remains unclear in P. chinensis. To elucidate the GAS biosynthesis and identify the related genes in P. chinensis, a comprehensive analysis of transcriptome and metabolome of roots, rhizomes, pseudobulbs and leaves were performed by using PacBio SMART, Illumina Hiseq and Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS). A total of 1,156 metabolites were identified by UPLC-MS/MS, of which 345 differential metabolites were mainly enriched in phenylpropanoid/phenylalanine, flavone and flavonol biosynthesis. The pseudobulbs make up nearly half of the fresh weight of the whole plant, and the GAS content in the pseudobulbs was also the highest in four tissues. Up to 23,105 Unigenes were obtained and 22,029 transcripts were annotated in the transcriptome analysis. Compared to roots, 7,787, 8,376 and 9,146 differentially expressed genes (DEGs) were identified in rhizomes, pseudobulbs and leaves, respectively. And in total, 80 Unigenes encoding eight key enzymes for GAS biosynthesis, were identified. Particularly, glycosyltransferase, the key enzyme of the last step in the GAS biosynthetic pathway had 39 Unigenes candidates, of which, transcript28360/f2p0/1592, was putatively identified as the most likely candidate based on analysis of co-expression, phylogenetic analysis, and homologous searching. The metabolomics and transcriptomics of pseudobulbs versus roots showed that 8,376 DEGs and 345 DEMs had a substantial association based on the Pearson's correlation. This study notably enriched the metabolomic and transcriptomic data of P. chinensis, and it provides valuable information for GAS biosynthesis in the plant.

Vitamin D Enhances Radiosensitivity of Colorectal Cancer by Reversing Epithelial-Mesenchymal Transition.

Colorectal cancer (CRC) is often resistant to conventional therapies. Previous studies have reported the anticancer effects of vitamin D in several cancers, its role in radiotherapy (RT) remains unknown. We found that 1α, 25-dihydroxyvitamin D3 (VD3), the biologically active form of vitamin D, had antitumor effect on CRC and sensitized CRC cells to ionizing radiation (IR). VD3 demonstrated synergistic effect in combination with IR, which were detected by colony formation and cell proliferation assay. Radiosensitivity restoration induced by VD3 was associated with a series of phenotypes, including apoptosis, autophagy, and epithelial-mesenchymal transition (EMT). Using proteomics, "regulation of cell migration" and "cadherin" were found to be obviously enriched GO terms. Moreover, cystatin D and plasminogen activator inhibitor-1 (PAI-1), the differentially expressed proteins, were associated with EMT. Next, we confirmed the contributions of these two genes in enhancing IR sensitivity of CRC cells upon inhibition of EMT. As determined by proteomics, the mechanism underlying such sensitivity involved partially block of JAK/STAT3 signaling pathway. Furthermore, VD3 also elicited sensitization to RT in xenograft CRC models without additional toxicity. Our study revealed that VD3 was able to act in synergy with IR both in vitro and in vivo and could also confer radiosensitivity by regulating EMT, thereby providing a novel insight for elevating the efficacy of therapeutic regimens.

Immune Response: A Missed Opportunity Between Vitamin D and Radiotherapy.

Radiotherapy (RT) is a mainstay treatment in several types of cancer and acts by mediating various forms of cancer cell death, although it is still a large challenge to enhance therapy efficacy. Radiation resistance represents the main cause of cancer progression, therefore, overcoming treatment resistance is now the greatest challenge for clinicians. Increasing evidence indicates that immune response plays a role in reprogramming the radiation-induced tumor microenvironment (TME). Intriguingly, radiation-induced immunosuppression possibly overwhelms the ability of immune system to ablate tumor cells. This induces an immune equilibrium, which, we hypothesize, is an opportunity for radiosensitizers to make actions. Vitamin D has been reported to act in synergistic with RT by potentiating antiproliferative effect induced by therapeutics. Additionally, vitamin D can also regulate the TME and may even lead to immunostimulation by blocking immunosuppression following radiation. Previous reviews have focused on vitamin D metabolism and epidemiological trials, however, the synergistic effect of vitamin D and existing therapies remains unknown. This review summarizes vitamin D mediated radiosensitization, radiation immunity, and vitamin D-regulated TME, which may contribute to more successful vitamin D-adjuvant radiotherapy.

Dual effects of active ERK in cancer: A potential target for enhancing radiosensitivity.

Ionizing radiation (IR) is an important cancer treatment approach. However, radioresistance eventually occurs, resulting in poor outcomes in patients with cancer. Radioresistance is associated with multiple signaling pathways, particularly pro-survival signaling pathways. The extracellular signal-regulated kinase 1/2 (ERK1/2) cascade is an important signaling pathway that initiates several cellular processes and is regulated by various stimuli, including IR. Although numerous studies have demonstrated the pro-survival effects of active ERK, activation of ERK has also been associated with cell death, indicating that radiosensitization may occur by ERK stimulation. In this context, the present review describes the associations between ERK signaling, cancer and IR, and discusses the association between ERK and its pro-survival function in cancer cells, including stimuli, molecular mechanisms, clinical use of inhibitors and underlying limitations. Additionally, the present review introduces the view that active ERK may induce cell death, and describes the potential factors associated with this process. This review describes the various outcomes induced by active ERK to prompt future studies to aim to enhance radiosensitivity in the treatment of cancer.

Hypoxia-induced autophagy promotes EGFR loss in specific cell contexts, which leads to cell death and enhanced radiosensitivity.

Treatment failure through radioresistance of tumors is associated with activation of the epidermal growth factor receptor (EGFR). Tumor cell proliferation, DNA-repair, hypoxia and metastases-formation are four mechanisms in which EGFR signaling has an important role. However, the effect of hypoxia on EGFR expression is still controversial. In this study, we demonstrated that hypoxia enhanced EGFR expression and sustained cell survival in SiHa, CAL 27 and A549 cells at both low and high cell desnities, while in MCF-7, MDA-MB-231 and HeLa cells, EGFR and cell survival were regulated by hypoxic treatment in a cell-density dependent manner: upregulated at low cell density and downregulated at high cell density. In MCF-7 and HeLa xenografts in nude mice, EGFR expression varied inversely with the pimonidazole level that was used as an indicator of hypoxia, accordant with the effect of hypoxia at high cell density in vitro. Hypoxia induced more remarkable cell autophagy at high cell density than at low cell density. Autophagy inhibitor 3MA, rather than proteasome inhibitor MG132 inhibited hypoxia-mediated EGFR loss and shifted cell death to cell survival in HeLa cells. The MCF7 cells' sensitivity to ionizing radiation (IR) under hypoxia was also conditional on the cell densities when the hypoxia treatment was introduced, inversely associated with the expression levels of EGFR. Altogether, hypoxia can decrease EGFR expression in some cell lines by enhancing autophagy at high cell density, leading to cell death and hypersensitivity to radiotherapy. This study may help to understand how hypoxia influences EGFR expression and radiosensitivity.

Inhibition of Autophagy Promoted Apoptosis and Suppressed Growth of Hepatocellular Carcinoma Upon Photothermal Exposure.

Photothermal therapy (PTT) is a recently developed and promising strategy for the treatment of hepatocellular carcinoma (HCC). However, apoptosis has been extensively investigated as the mechanism of the underlying effect of PTT on cancer to date. Here, we explored alternative mechanisms of these therapeutic effects, including the activation of cell-cycle arrest and autophagy during PTT in addition to apoptosis under mild temperature. We treated the HCC cell line HepG2 with polydopamine (PDA)-coated branched Au-Ag nanoparticles at various concentrations along with PTT using an 808-nm laser. Apoptosis was evaluated based on flow cytometry, western blot analysis of apoptosis related proteins (BAX, BCL2, caspase 3), Hoechst staining, and TUNEL staining. To explore the role of autophagy, we treated cells with the autophagy inhibitor chloroquine diphosphate. Enhancement of apoptosis by PTT with nanoparticle treatment was observed after autophagy was inhibited. Moreover, inhibition of autophagy markedly enhance the suppression of tumor growth in vivo in a HepG2 mouse xenograft model. These results suggest that further exploration of the mechanism of PTT can help guide its clinical application, and that autophagy inhibition combined with PTT could be a promising strategy for HCC treatment.

Photothermal exposure of polydopamine-coated branched Au-Ag nanoparticles induces cell cycle arrest, apoptosis, and autophagy in human bladder cancer cells.

PURPOSE: Polydopamine-coated branched Au-Ag nanoparticles (Au-Ag@PDA NPs) exhibit good structural stability, biocompatibility, and photothermal performance, along with potential anticancer efficacy. Here, we investigated the cytotoxicity of Au-Ag@PDA NPs against human bladder cancer cells (T24 cells) in vitro and in vivo, as well as the underlying molecular mechanisms of photothermal therapy-induced T24 cell death. MATERIALS AND METHODS: T24 cells were treated with different doses of Au-Ag@PDA NPs followed by 808 nm laser irradiation, and the effects on cell proliferation, cell cycle, apoptosis, and autophagy were analyzed. To confirm the mechanisms of inhibition, real-time PCR and Western blot analysis were used to evaluate markers of cell cycle, apoptosis, autophagy, and the AKT/ERK signaling pathway. Moreover, we evaluated the effects of the treatment on mitochondrial membrane potential and ROS generation to confirm the underlying mechanisms of inhibition. Finally, we tested the T24 tumor inhibitory effects of Au-Ag@PDA NPs plus laser irradiation in vivo using a xenograft mouse model. RESULTS: Au-Ag@PDA NPs, with appropriate laser irradiation, dramatically inhibited the proliferation of T24 cells, altered the cell cycle distribution by increasing the proportion of cells in the S phase, induced cell apoptosis by activating the mitochondria-mediated intrinsic pathway, and triggered a robust autophagy response in T24 cells. Moreover, Au-Ag@PDA NPs decreased the expression of phosphorylated AKT and ERK and promoted the production of ROS that function upstream of apoptosis and autophagy. In addition, Au-Ag@PDA NP-mediated photothermolysis also significantly suppressed tumor growth in vivo. CONCLUSION: This preclinical study can provide a mechanistic basis for Au-Ag@PDA NP-mediated photothermal therapy toward promotion of this method in the clinical treatment of bladder cancer.

CMTM3 decreases EGFR expression and EGF-mediated tumorigenicity by promoting Rab5 activity in gastric cancer.

CMTM3 (CKLF-like MARVEL transmembrane domain containing 3), a tumor suppressor gene, is involved in multiple types of malignancies. CMTM3 knockdown promotes metastasis of gastric cancer via the STAT3/Twist1/EMT signaling pathway. Strong epidermal growth factor receptor1 (EGFR) expression is significantly associated with tumor metastasis and poor outcomes of gastric cancer patients. In this paper, we show that CMTM3 suppresses epidermal growth factor (EGF)-mediated migration and STAT3 signaling, downregulates EGFR expression via accelerating EGFR degradation in gastric cancer cells. CMTM3 colocalizes with early endosome markers Rab5 and EEA1. Co-immunoprecipitation (Co-IP) assay further confirms that CMTM3 interacts with Rab5. More importantly, CMTM3 markedly increases Rab5 activity. The suppressive effects of CMTM3 on EGFR expression and EGF-mediated migration can be abrogated by the siRNA against Rab5. Finally, we found that the C-terminal region of CMTM3 plays more important roles in the tumor suppressive effects of CMTM3. Overall, this study demonstrates that CMTM3 decreases EGFR expression, facilitates EGFR degradation, and inhibits the EGF-mediated tumorigenicity of gastric cancer cells via enhancing Rab5 activity.

Knockdown of CMTM3 promotes metastasis of gastric cancer via the STAT3/Twist1/EMT signaling pathway.

CMTM3 (CKLF-like MARVEL transmembrane domain containing 3) possesses tumor suppressor properties in multiple types of malignancies. Restoration of CMTM3 significantly inhibits the metastasis of gastric cancer, and its expression level is correlated with prognosis. However, the physiological effects and the mechanism of CMTM3 remain unknown. Here, we suppress CMTM3 expression by shRNA to explore its endogenous effects and its mechanism of action in gastric cancer. Stable knockdown of CMTM3 promotes cell migration, invasion and tumor metastasis, increases MMP2 expression and enhances MMP2 activity. CMTM3 inhibits EMT along with the upregulation of E-cadherin and the downregulation of N-cadherin, Vimentin and Twist1. It has no obvious effects on Zeb1 and Snail. CMTM3 suppresses the phosphorylation of STAT3 but not Akt. More importantly, the EMT phenotype and cell migration induced by CMTM3 knockdown can be reversed by the Jak2/STAT3 inhibitor JSI-124 or by siRNA against STAT3 or Twist1. Overall, this study demonstrates that knockdown of CMTM3 promotes the metastasis of gastric cancer through the STAT3/Twist1/EMT pathway.

CMTM7 knockdown increases tumorigenicity of human non-small cell lung cancer cells and EGFR-AKT signaling by reducing Rab5 activation.

The dysregulation of epidermal growth factor receptor (EGFR) signaling has been well documented to contribute to the progression of non-small cell lung cancer (NSCLC), the leading cause of cancer death in the world. EGF-stimulated EGFR activation induces receptor internalization and degradation, which plays an important role in EGFR signaling. This process is frequently deregulated in cancer cells, leading to enhanced EGFR levels and signaling. Our previous study on CMTM7 is only limited to a brief description of the relationship of overexpressed CMTM7 with EGFR-AKT signaling. The biological functions of endogenous CMTM7 and its molecular mechanism remained unclear. In this study, we show that the stable knockdown of CMTM7 augments the malignant potential of NSCLC cells and enhances EGFR-AKT signaling by decreasing EGFR internalization and degradation. Mechanistically, CMTM7 knockdown reduces the activation of Rab5, a protein known to be required for early endosome fusion. In NSCLC, the loss of CMTM7 would therefore serve to sustain aberrant EGFR-mediated oncogenic signaling. Together, our findings highlight the role of CMTM7 in the regulation of EGFR signaling in tumor cells, revealing CMTM7 as a novel molecule related to Rab5 activation.

CSBF/C10orf99, a novel potential cytokine, inhibits colon cancer cell growth through inducing G1 arrest.

Cytokines are soluble proteins that exert their functions by binding specific receptors. Many cytokines play essential roles in carcinogenesis and have been developed for the treatment of cancer. In this study, we identified a novel potential cytokine using immunogenomics designated colon-derived SUSD2 binding factor (CSBF), also known as chromosome 10 open reading frame 99 (C10orf99). CSBF/C10orf99 is a classical secreted protein with predicted molecular mass of 6.5 kDa, and a functional ligand of Sushi Domain Containing 2 (SUSD2). CSBF/C10orf99 has the highest expression level in colon tissue. Both CSBF/C10orf99 and SUSD2 are down-regulated in colon cancer tissues and cell lines with different regulation mechanisms. CSBF/C10orf99 interacts with SUSD2 to inhibit colon cancer cell growth and induce G1 cell cycle arrest by down-regulating cyclin D and cyclin-dependent kinase 6 (CDK6). CSBF/C10orf99 displays a bell-shaped activity curve with the optimal effect at ~10 ng/ml. Its growth inhibitory effects can be blocked by sSUSD2-Fc soluble protein. Our results suggest that CSBF/C10orf99 is a novel potential cytokine with tumor suppressor functions.

Change of CMTM7 expression, a potential tumor suppressor, is associated with poor clinical outcome in human non-small cell lung cancer.

BACKGROUND: CKLF-like MARVEL transmembrane domain-containing 7 (CMTM7) located at 3p22.3, is a frequent deletion site and a tumor suppressor gene (TSG) locus in many cancer, which suggests CMTM7 may be a potential TSG. The aim of this study was to investigate the correlations of CMTM7 expression and survival rate in patients with non-smallcell lung cancer (NSCLC). METHODS: Surgical specimens of 180 cases with pathologically confirmed NSCLC were grouped into 18 tissue microarray slides. CMTM7 expression in these specimens were detected by immunohistochemistry staining and representative cases were confirmed by Western blotting. Univariate and multivariate analyses were performed to identify the association of CMTM7 expression with pathological features and survival of patients with NSCLC. RESULTS: A total of 78.9% of the 180 patients had variations of CMTM7 protein expression, either up-regulated or down-regulated. Univariate analysis showed that the patients' survival rate after surgery was highly correlated with CMTM7 expression (P = 0.0091). In addition, prognostic factors were examined by multivariate Cox regression analysis, and results suggested that CMTM7 expression was a unique prognostic factor in NSCLC survival. CONCLUSIONS: The CMTM7 expression may be related to survival of patients with NSCLC and a unique prognostic factor. CMTM7 may play an important role in NSCLC development.