Reproductive organ development is one of the most important steps in the life cycle of plants. Studies using core eudicot species like thale cress (Arabidopsis thaliana) and snapdragon (Antirrhinum majus) have shown that MADS domain transcription factors belonging to the AGAMOUS (AG) subfamily regulate the identity of stamens, carpels, and ovules and that they are important for floral meristem determinacy. Here, we investigate the genetic interactions between the four rice (Oryza sativa) AG subfamily members, MADS3, MADS13, MADS21, and MADS58. Our data show that, in contrast with previous reports, MADS3 and MADS58 determine stamen and carpel identity and, together with MADS13, are important for floral meristem determinacy. In the mads3 mads58 double mutant, we observed a complete loss of reproductive organ identity and massive accumulation of lodicules in the third and fourth floral whorls. MADS21 is an AGL11 lineage gene whose expression is not restricted to ovules. Instead, its expression profile is similar to those of class C genes. However, our genetic analysis shows that MADS21 has no function in stamen, carpel, or ovule identity determination.

Rice (Oryza sativa) has unique floral patterns that contribute to grain yield. However, the molecular mechanism underlying the specification of floral organ identities in rice, particularly the interaction among floral homeotic genes, remains poorly understood. Here, we show that the floral homeotic gene OsMADS16 (also called SUPERWOMAN1, SPW1, a B-class gene) acts together with the rice C-class genes OsMADS3 and OsMADS58 in specifying floral organ patterning. OsMADS16 and the two C-class genes have an overlapping expression pattern in the third whorl founder cells. Compared with the single mutants, both spw1-1 osmads3-4 and spw1-1 osmads58 double mutants exhibit additional whorls of glume-like organs within the flower, particularly an extra whorl of six glume-like structures formed at the position of the wild-type stamens. These ectopic glume-like structures were shown to have palea identity through cellular observation and in situ hybridization analysis using marker genes. Our results suggest that Band C-class genes play a key role in suppressing indeterminate growth within the floral meristem, particularly whorl-3 primordia. We also hypothesize that, in contrast to previous assumptions, the specialized spikelet organ in rice, the palea, is the counterpart of the sepal in eudicots, and the lemma is homologous to the bract.

Our findings identified VAMP8 as a novel oncogene by promoting cell proliferation and therapeutic resistance in glioma. Targeting VAMP8 may serve as a potential therapeutic regimen for the treatment of glioma.

Glioma is the most malignant brain tumor and glioblastoma (GBM) is the most aggressive type. The involvement of N-myc (and STAT) interactor (NMI) in tumorigenesis was sporadically reported but far from elucidation. This study aims to investigate roles of NMI in human glioma. Three independent cohorts, the Chinese tissue microarray (TMA) cohort (N = 209), the Repository for Molecular Brain Neoplasia Data (Rembrandt) cohort (N = 371) and The Cancer Genome Atlas (TCGA) cohort (N = 528 or 396) were employed. Transcriptional or protein levels of NMI expression were significantly increased according to tumor grade in all three cohorts. High expression of NMI predicted significantly unfavorable clinical outcome for GBM patients, which was further determined as an independent prognostic factor. Additionally, expression and prognostic value of NMI were associated with molecular features of GBM including PTEN deletion and EGFR amplification in TCGA cohort. Furthermore, overexpression or depletion of NMI revealed its regulation on G1/S progression and cell proliferation (both in vitro and in vivo), and this effect was partially dependent on STAT1, which interacted with and was regulated by NMI. These data demonstrate that NMI may serve as a novel prognostic biomarker and a potential therapeutic target for glioblastoma.

Frequent loss of multiple regions in short arm of chromosome 3 is found in various tumors including gastric cancer (GC). RNA binding motif, single-stranded interacting protein 3 (RBMS3) is a tumor suppressor gene located in this region and mediates cancer angiogenesis. However, the role of RBMS3 in GC remains unclear.To evaluate whether RBMS3, together with HIF1A, another key regulator of angiogenesis, predicts GC prognosis, the levels of RBMS3 and HIF1A were first examined by quantitative PCR (qPCR) and western blot from 27 fresh frozen GC and paired normal gastric tissues and then tested by immunohistochemistry (IHC) from 191 GC and 46 normal controls. Moreover, uni- and multivariate analysis were employed to assess the correlations between their levels and microvessel density (MVD) and clinical prognosis. To further identify RBMS3 function in vitro, cell proliferation assay, clonogenic assay, flow cytometry analysis and endothelial cell tube formation assay were employed.We found that RBMS3 level was decreased, whereas HIF1A was elevated in GC. Furthermore, we demonstrated that RBMS3 was an independent prognostic factor and the levels of RBMS3 and HIF1A were associated with GC angiogenesis and histopathological differentiation: patients with lower RBMS3 level and higher nuclear HIF1A expression had poorer prognosis. Besides, gain- and loss-of-function study revealed RBMS3 regulation on G1/S progression, cell proliferation and the tube formation of human umbilical vein endothelial cells (HUVECs) in vitro. These findings implicated that RBMS3 and nuclear HIF1A could act as prognostic biomarkers and therapeutic targets for GC.

Glioma is the most aggressive and malignant primary brain tumor in adults. In the present study, we identified a vital oncoprotein, capping actin protein, gelsolin-like (CapG), and investigated its roles in the prognosis, proliferation and metastasis in glioma. The mRNA and protein levels of CapG were significantly increased in human glioma, and higher CapG expression was an independent prognostic factor for predicting unfavorable prognosis. The expression level of CapG was found to be associated with several common molecular features of glioblastoma (GBM; WHO grade IV glioma) in The Cancer Genome Atlas (TCGA) cohort. When analyzing the prognosis of GBM patients according to these molecular features, we observed that the prognostic value of CapG was affected by amplification of CDK6 or EGFR. However, overexpression of CapG markedly promoted cell growth in vitro, while depletion of CapG significantly inhibited cell proliferation by blocking the cell cycle in G1/S transition. Moreover, CapG manipulation in glioma cell lines U87 and U251 showed CapG-dependent cellular migration and invasiveness. These data suggest that CapG may serve as a prognostic biomarker with potentially important therapeutic implications for glioma.

Background: LGALS3 promotes tumor progression in diverse cancers. However, the involvement of LGALS3 in glioblastoma has not yet been broadly illuminated. Methods: Microarray was performed to detect the gene expression profiles of radioresistance in T98G cells and identified a universally upregulated gene, LGALS3. The impact of LGALS3 on the survival of glioblastoma cells facing ionizing irradiation or temozolomide was investigated by the Cell Counting Kit-8 (CCK-8). A total of 120 glioblastoma cases were collected to analyze the relationship between LGALS3 expression and patient prognosis. Another 961 patients with glioma and 1,351 healthy controls were recruited to study the association of SNPs across the LGALS3 gene with glioblastoma susceptibility. The functional SNP sites were also studied in cellular experiments. Results: An effective protection of LGALS3 from ionizing irradiation or temozolomide-induced cell death in T98G and U251 cells was found. In addition, high expression of LGALS3 could work as an independent risk factor for survival of patients with glioblastoma. Two SNP sites (rs4644 and rs4652) across the LGALS3 gene were associated with increased risk for glioblastoma, and the C allele of rs4652 and the A allele of rs4644 could enhance glioblastoma resistance to radio-chemotherapy, but not cell proliferation. Conclusions: Our results suggest that LGALS3 is an important biomarker influencing glioblastoma risk and prognosis and a potential target for treating the malignancy, especially ones with resistance against the standard therapy. Impact: LGALS3 promotes glioblastoma cells' resistance to ionizing irradiation and temozolomide and predicts poor prognosis. Targeting LGALS3 may limit the therapeutic resistance in glioblastoma and increase patient survival.

Our results showed for the first time that overexpression of eEF1A2 was correlated with worse outcomes in gastric cancer patients, suggesting its critical roles in the carcinogenesis of gastric cancer.