Transfer RNA-derived fragment tRF-23-Q99P9P9NDD promotes progression of gastric cancer by targeting ACADSB. / 转移RNA衍生片段tRF-23-Q99P9P9NDD通过靶向ACADSB促进胃癌进展.

Gastric cancer (GC) is one of the most common gastrointestinal tumors. As a newly discovered type of non-coding RNAs, transfer RNA (tRNA)|-derived small RNAs (tsRNAs) play a dual biological role in cancer. Our previous studies have demonstrated the potential of tRF-23-Q99P9P9NDD as a diagnostic and prognostic biomarker for GC. In this work, we confirmed for the first time that tRF-23-Q99P9P9NDD can promote the proliferation, migration, and invasion of GC cells in vitro. The dual luciferase reporter gene assay confirmed that tRF-23-Q99P9P9NDD could bind to the 3' untranslated region (UTR) site of acyl-coenzyme A dehydrogenase short/branched chain (ACADSB). In addition, ACADSB could rescue the effect of tRF-23-Q99P9P9NDD on GC cells. Next, we used Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) to find that downregulated ACADSB in GC may promote lipid accumulation by inhibiting fatty acid catabolism and ferroptosis. Finally, we verified the correlation between ACADSB and 12 ferroptosis genes at the transcriptional level, as well as the changes in reactive oxygen species (ROS) levels by flow cytometry. In summary, this study proposes that tRF-23-Q99P9P9NDD may affect GC lipid metabolism and ferroptosis by targeting ACADSB, thereby promoting GC progression. It provides a theoretical basis for the diagnostic and prognostic monitoring value of GC and opens up new possibilities for treatment.

A novel hypoxia-associated gene signature for prognosis prediction in head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the most common malignant tumor of head and neck, which seriously threatens human life and health. However, the mechanism of hypoxia-associated genes (HAGs) in HNSCC remains unelucidated. This study aims to establish a hypoxia-associated gene signature and the nomogram for predicting the prognosis of patients with HNSCC. METHODS: Previous literature reports provided a list of HAGs. The TCGA database provided genetic and clinical information on HNSCC patients. First, a hypoxia-associated gene risk model was constructed for predicting overall survival (OS) in HNSCC patients and externally validated in four GEO datasets (GSE27020, GSE41613, GSE42743, and GSE117973). Then, immune status and metabolic pathways were analyzed. A nomogram was constructed and assessed the predictive value. Finally, experimental validation of the core genes was performed by qRT-PCR. RESULTS: A HNSCC prognostic model was constructed based on 8 HAGs. This risk model was validated in four external datasets and exhibited high predictive value in various clinical subgroups. Significant differences in immune cell infiltration levels and metabolic pathways were found between high and low risk subgroups. The nomogram was highly accurate for predicting OS in HNSCC patients. CONCLUSIONS: The 8 hypoxia-associated gene signature can serve as novel independent prognostic indicators in HNSCC patients. The nomogram combining the risk score and clinical stage enhanced predictive performance in predicting OS compared to the risk model and clinical characteristics alone.

High expression of GPR176 predicts poor prognosis of gastric cancer patients and promotes the proliferation, migration, and invasion of gastric cancer cells.

G-protein-coupled receptors (GPCRs) are the most prominent family of cell surface receptors, which can regulate various biological functions and play an essential role in many diseases. GPR176 is a member of the GPCRs family and has been rarely studied in cancer. We aim to investigate the diagnostic and prognostic value of GPR176 in gastric cancer (GC) and explore its potential mechanism. Through the TCGA database and real-time quantitative PCR, we found that the expression level of GPR176 was significantly increased in GC and had good value in the diagnosis and prognosis of GC. Vitro experiments revealed that GPR176 could promote the proliferation, migration, and invasion of GC cells and may be involved in regulating multiple tumors and immune-related signaling pathways. In addition, we found that GPR176 is associated with GC immune infiltration and may affect the immune efficacy of GC patients. In summary, the high GPR176 expression level was associated with poor prognosis, more robust immune infiltration, and worse immunotherapy efficacy in GC patients, suggesting that GPR176 may be an immune-related biomarker for GC that can promote the proliferation, migration, and invasion of GC cells.

Circulating circular RNA hsa_circ_0023179 acts as a diagnostic biomarker for non-small-cell lung cancer detection.

BACKGROUND: Lung cancer, the most prevalent cancer-related death worldwide, still lacks the means for early diagnosis. Because of the unique properties of the loop that make it stable in body fluids, circular RNAs (circRNAs) as a biomarker becomes a possibility. This research purposed to explore whether hsa_circ_0023179 can be applied as a possible biomarker for the early diagnosis and prognosis of non-small cell lung cancer (NSCLC). METHODS: hsa_circ_0023179 was screened by high-throughput sequencing of three pairs of NSCLC tissues and their surrounding tissues. Agarose gel electrophoresis (AGE), Sanger sequencing, exonuclease digestion assay, and actinomycin D were used to affirm the molecular properties of circRNA. Precision determination was performed by placement at room temperature and multiple freeze-thawing test for methodological evaluation. The expression of hsa_circ_0023179 in tissues, serum, and cells was determined by quantitative real-time polymerase chain reaction (qRT-PCR) to establish the receiver operating characteristic (ROC) curve to assess the diagnostic efficacy of hsa_circ_0023179. RESULTS: hsa_circ_0023179 conforms to the basic properties of circRNA, and the detection method of hsa_circ_0023179 has good stability and repeatability. Its expression was connected to histological type, TNM stage, lymph node metastasis, and distal metastasis in NSCLC tissues, serum, and cells. Compared with traditional tumor markers with higher sensitivity and specificity. A combined diagnosis can significantly improve the diagnostic value. The decrease in postoperative expression level suggests some potential for dynamic monitoring. CONCLUSION: hsa_circ_0023179 might be a promising novel serum marker for the detection and prediction of NSCLC.

Comprehensive Evaluation of Serum tRF-17-WS7K092 as a Promising Biomarker for the Diagnosis of Gastric Cancer.

Background: Gastric cancer (GC) is a malignant tumor of the gastrointestinal system. Since the early symptoms of GC are not obvious and lack efficient diagnostic markers, it is urgent to find new diagnostic markers with good sensitivity and specificity. tRNA-derived small RNAs (tsRNAs) are an emerging class of small noncoding RNAs with good abundance in body fluids. We aim to find new tsRNAs as biomarkers for GC diagnosis. Methods: High-throughput sequencing was used to identify differentially expressed tsRNAs in GC tissues, and quantitative real-time PCR was used to detect the expression level of tRF-17-WS7K092. Agarose gel electrophoresis and Sanger sequencing were performed to verify the characteristics of tRF-17-WS7K092. The diagnostic efficacy of tRF-17-WS7K092 was analyzed by the receiver operating characteristic curve. Results: In this study, the expression levels of tRF-17-WS7K092 were significantly increased in GC tissues, cells, and serum. After GC surgery, the expression level of serum tRF-17-WS7K092 decreased, and its high expression was associated with low survival rates. In addition, the expression level of serum tRF-17-WS7K092 was correlated with the T stage, TNM stage, lymph node metastasis, and nerve/vascular invasion and could distinguish GC patients from gastritis patients and healthy donors as well. Conclusions: The expression of serum tRF-17-WS7K092 was significantly increased in GC and decreased after GC surgery, suggesting that serum tRF-17-WS7K092 may serve as a promising biomarker for the diagnostic and prognostic monitoring of GC.

m6A-modified circRNAs: detections, mechanisms, and prospects in cancers.

Circular RNAs (circRNAs) have become a research hotspot in recent years with their universality, diversity, stability, conservativeness, and spatiotemporal specificity. N6-methyladenosine (m6A), the most abundant modification in the eukaryotic cells, is engaged in the pathophysiological processes of various diseases. An increasing amount of evidence has suggested that m6A modification is common in circRNAs and is associated with their biological functions. This review summarizes the effects of m6A modification on circRNAs and their regulation mechanisms in cancers, providing some suggestions of m6A-modified circRNAs in cancer therapy.

Transfer RNA-derived small RNA: an emerging small non-coding RNA with key roles in cancer.

Transfer RNAs (tRNAs) promote protein translation by binding to the corresponding amino acids and transporting them to the ribosome, which is essential in protein translation. tRNA-derived small RNAs (tsRNAs) are derived fragments of tRNAs that are cleaved explicitly under certain conditions. An increasing amount of research has demonstrated that tsRNAs have biological functions rather than just being degradation products. tsRNAs can exert functions such as regulating gene expression to influence cancer progression. Their dysregulation is closely associated with various cancers and can serve as diagnostic and prognostic biomarkers for cancer. This review summarizes the generation, classification, and biological functions of tsRNAs, and highlights the roles of tsRNAs in different cancers and their applications as tumor markers.

Evaluation of serum tRF-23-Q99P9P9NDD as a potential biomarker for the clinical diagnosis of gastric cancer.

BACKGROUND: Gastric cancer (GC) is one of the diseases that endanger human health with high morbidity and mortality. The positive rates of traditional biomarkers in the diagnosis of GC are low, so it is necessary to find biomarkers with high sensitivity to increase the detection rate. tRNA-derived small RNAs (tsRNAs) are novel small non-coding RNAs with specific biological functions and aberrant expression in cancer. In this study, we focused on the potential of tRNA-derived small RNAs as GC biomarkers. METHODS: The differentially expressed tsRNAs in three pairs of GC tissues were screened with high-throughput sequencing and verified using the TCGA database and Quantitative real-time PCR. The methodological evaluation of tRF-23-Q99P9P9NDD was verified by agarose gel electrophoresis, RIN evaluation, and Sanger sequencing. The Chi-square test was used to evaluate the relationship between the tRF-23-Q99P9P9NDD expression and clinicopathological parameters. Kaplan-Meier survival analysis was used to evaluate the effect of the tRF-23-Q99P9P9NDD expression on survival. Additionally, the receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficacy of tRF-23-Q99P9P9NDD in GC. RESULTS: Differential expression of serum tRF-23-Q99P9P9NDD could distinguish GC patients from gastritis patients and healthy donors. Chi-square test showed that high expression of tRF-23-Q99P9P9NDD was significantly associated with T stage, lymph node metastasis, TNM stage, and nerve/vascular invasion. Kaplan-Meier curve showed that patients with high expression of tRF-23-Q99P9P9NDD had a lower survival rate than patients with low expression of this biomarker. ROC analysis showed that, compared with conventional biomarkers, the efficacy of tRF-23-Q99P9P9NDD was higher, which was improved by the combination of biomarkers, and even in the early stages. Finally, we preliminarily predicted the downstream of tRF-23-Q99P9P9NDD in GC cells. CONCLUSIONS: The expression of tRF-23-Q99P9P9NDD in GC serum can identify GC patients, and it has higher efficacy than conventional biomarkers even in the early stages. Furthermore, tRF-23-Q99P9P9NDD can monitor the postoperative conditions of GC patients.

The expression of heat shock protein A12B (HSPA12B) in non-Hodgkin's lymphomas.

BACKGROUND: Heat shock protein A12B (HSPA12B) plays a considerable protective role for cells, tissues, and organs against various noxious conditions. However, the expression of HSPA12B in cancer biology remains controversial. This study aimed to investigate the expression of HSPA12B and its role in cell adhesion mediated drug resistance (CAM-DR) of non-Hodgkin's lymphoma (NHL). METHODS: In this study, the expression of HSPA12B in NHL was determined by immunohistochemical, and the effect of HSPA12B expression on the prognosis of NHL was analyzed by Kaplan-Meier curves. Then, the transfection technique was used to research the effect of HSPA12B in cell apoptosis. The most important was to study the expression changes of HSPA12B in the adhesion model and the effect of overexpression of HSPA12B on CAM-DR. RESULTS: We analyzed the relationship between the expression levels of HSPA12B and clinical parameters in NHL. The expression of HSPA12B was directly related to the different NHL variants. We overexpressed HSPA12B in 2 NHL cell lines and found a subsequent reduction in apoptosis. More specifically, we used an adhesion assay to demonstrate that HSPA12B expression was induced in NHL cells when they adhered to fibronectin (FN) or bone marrow stroma cells (BMSCs). Finally, it was revealed that HSPA12B overexpression enhances CAM-DR. CONCLUSIONS: Our data suggest that HSPA12B may play a functional role in CAM-DR and is thus a potential novel target for NHL treatment.

Elucidating the Role of Serum tRF-31-U5YKFN8DYDZDD as a Novel Diagnostic Biomarker in Gastric Cancer (GC).

BACKGROUND: Gastric cancer (GC) is one of the malignant tumors with the highest morbidity and mortality in the world. Early diagnosis combined with surgical treatment can significantly improve the prognosis of patients. Therefore, it is urgent to seek higher sensitivity and specificity biomarkers in GC. tRNA-derived small RNAs are a new non-coding small RNA that widely exists in tumor cells and body fluids. In this study, we explore the expression and biological significance of tRNA-derived small RNAs in GC. MATERIALS AND METHODS: First of all, we screened the differentially expressed tRNA-derived small RNAs in tumor tissues by high-throughput sequencing. Agarose gel electrophoresis (AGE), Sanger sequencing, and Nuclear and Cytoplasmic RNA Separation Assay were used to screen tRF-31-U5YKFN8DYDZDD as a potential tumor biomarker for the diagnosis of GC. Then, we detected the different expressions of tRF-31-U5YKFN8DYDZDD in 24 pairs of GC and paracancerous tissues, the serum of 111 GC patients at first diagnosis, 89 normal subjects, 48 superficial gastritis patients, and 28 postoperative GC patients by quantitative real-time PCR (qRT-PCR). Finally, we used the receiver operating characteristic (ROC) curve to analyze its diagnostic efficacy. RESULTS: The expression of tRF-31-U5YKFN8DYDZDD has good stability and easy detection. tRF-31-U5YKFN8DYDZDD was highly expressed in tumor tissue, serum, and cell lines of GC, and the expression was significantly related to TNM stage, depth of tumor invasion, lymph node metastasis, and vascular invasion. The expression of serum tRF-31-U5YKFN8DYDZDD in the GC patients decreased after the operation (P = 0.0003). Combined with ROC curve analysis, tRF-31-U5YKFN8DYDZDD has better detection efficiency than conventional markers. CONCLUSIONS: The expressions of tRF-31-U5YKFN8DYDZDD in the tumor and paracancerous tissues, the serum of GC patients and healthy people, and the serum of GC patients before and after operation were different. tRF-31-U5YKFN8DYDZDD is not only a diagnostic biomarker of GC but also a predictor of poor prognosis.

CAM-DR: Mechanisms, Roles and Clinical Application in Tumors.

Despite the continuous improvement of various therapeutic techniques, the overall prognosis of tumors has been significantly improved, but malignant tumors in the middle and advanced stages still cannot be completely cured. It is now evident that cell adhesion-mediated resistance (CAM-DR) limits the success of cancer therapies and is a great obstacle to overcome in the clinic. The interactions between tumor cells and extracellular matrix (ECM) molecules or adjacent cells may play a significant role in initiating the intracellular signaling pathways that are associated with cell proliferation, survival upon binding to their ligands. Recent studies illustrate that these adhesion-related factors may contribute to the survival of cancer cells after chemotherapeutic therapy, advantageous to resistant cells to proliferate and develop multiple mechanisms of drug resistance. In this review, we focus on the molecular basis of these interactions and the main signal transduction pathways that are involved in the enhancement of the cancer cells' survival. Furthermore, therapies targeting interactions between cancer cells and their environment to enhance drug response or prevent the emergence of drug resistance will also be discussed.

Comprehensive Assessment of Serum hsa_circ_0070354 as a Novel Diagnostic and Predictive Biomarker in Non-small Cell Lung Cancer.

Background: More and more studies have shown that circular RNAs (circRNAs) play an essential role in the occurrence and development of tumors. Hence, they can be used as biomarkers to assist in diagnosing tumors. This study focuses on exploring the role of circular RNA (hsa_circ_0070354) in the diagnosis and prognosis of non-small cell lung cancer (NSCLC). Materials and Methods: First of all, high-throughput sequencing was used to find the difference in the expression of circular RNA between NSCLC and adjacent tissues. The circRNAs with higher differences in expression were selected to verify their expressions in tissues, cells, and serum using qRT-PCR. Secondly, the hsa_circ_0070354 with a significant difference was chosen as the research goal, and the molecular properties were verified by agarose gel electrophoresis and Sanger sequencing, etc. Then, actinomycin D and repeated freeze-thaw were used to explore the stability and repeatability of hsa_circ_0070354. Finally, the expression of hsa_circ_0070354 in serum of 133 patients with NSCLC and 97 normal donors was detected, and its sensitivity, specificity, and prognosis as tumor markers were statistically analyzed. Results: Hsa_circ_0070354 was highly expressed in tissues, cells, and serum of NSCLC, and it has the characteristics of sensitivity, stability, and repeatability. The ROC curve indicates that hsa_circ_0070354 is superior to conventional tumor markers in detecting NSCLC, and the combined diagnosis is of more significance in the diagnosis. The high expression of hsa_circ_0070354 is closely related to the late-stage, poor differentiation of the tumor and the short survival time of the patients, which is an independent indicator of poor prognosis. Conclusion: Hsa_circ_0070354 is not only a novel sensitive index for the diagnosis of NSCLC but also a crucial marker for bad biological behavior.

Development and Validation of Prognostic Survival Nomograms for Patients with Anal Canal Cancer: A SEER-Based Study.

OBJECTIVE: Anal canal cancer is a rare malignancy with increasing incidence in recent times. This study aimed to develop two nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) of patients with anal canal cancer. METHODS: Information of patients with anal canal cancer from 2004 to 2015 was extracted from the surveillance, epidemiology, and end results (SEER) database. Cox analysis was used to select the risk factors for prognosis, and nomograms were constructed using the R software. The C-index, area under the curve (AUC) of time-dependent receiver operating characteristic (ROC) curves, calibration plot and decision curve analysis (DCA) were used to assess the clinical utility of the nomograms. RESULTS: A total of 2458 patients with malignant tumours of the anal canal were screened out. Sex, age, marital status, histological type, grade, tumour size, AJCC stage, SEER stage and chemotherapy were independent prognostic factors for OS, whereas sex, age, race, histological type, grade, tumour size, AJCC stage, SEER stage and radiotherapy were independent prognostic factors for CSS. In the training cohort, the C-index value for OS nomogram was 0.73 (95% CI, 0.69-0.77), and the AUC values that predicted the 1-, 3- and 5-year survival rates were 0.764, 0.758 and 0.760, respectively, whereas the C-index value for CSS nomogram model was 0.74 (95% CI, 0.69-0.79), and the AUC values were 0.763, 0.769 and 0.763, respectively. The calibration plot and DCA curves demonstrated good prediction performance of the model in both the training and validation cohorts. CONCLUSION: The established nomogram is a visualisation tool that can effectively predict the OS and CSS of patients with anal canal cancer.

Role of Apg-1 in HSF1 activation and bortezomib sensitivity in myeloma cells.

Exposure of cells to bortezomib (BTZ) could activate heat shock protein (HSP) expression, which is regulated mainly by heat shock factor 1 (HSF1). We determined the role of Apg-1 (HSPA4L, a member of the HSP110 family) in HSF1 activation and bortezomib sensitivity by silencing HSF1 in multiple myeloma (MM) cells. We observed that the Apg-1 protein level was upregulated as BTZ concentration increased. To investigate the mechanism underlying Apg-1 induction, we evaluated the HSF1 translocation and found BTZ-inducible transposition to the nucleus of HSF1. In addition, cleaved caspase 3 and PARP might account for increased BTZ sensitivity on Apg-1 silencing. Furthermore, silencing HSF1 with shRNA or triptolide resulted in significant BTZ sensitivity. It had a more profound effect on cell death caused by BTZ when myeloma cells were adherent to bone marrow stromal cell lines (Hs-5). In summary, we found that Apg-1 knockdown sensitized myeloma cells to bortezomib treatment, which may provide a new approach in multiple myeloma treatment.

ß-TrCP1 promotes cell proliferation via TNF-dependent NF-κB activation in diffuse large B cell lymphoma.

Diffuse large B cell lymphoma (DLBCL), a heterogeneous group of invasive disease, is the most common type of B-cell non-Hodgkin's lymphomas. The mechanism of its development is closely related to the constitutive activation of NF-κB. In this study, we investigated the function and the mechanism of ß-TRCP1 in DLBCL. CCK8 and EdU assays showed that ß-TRCP1 could promote the growth of DLBCL cells under the stimulation of TNFα. Furthermore, overexpression of ß-TRCP1 enhanced NF-κB activation in the presence of TNFα. Moreover, ectopic expression of ß-TRCP1 decreased IκB-α expression but increased phospho-p65 expression. In addition, ß-TRCP1 promoted cell cycle progression by accelerating G1-S phase transition. We also found that silencing of ß-TrCP1 increased mitoxantrone-induced cell growth arrest and apoptosis. Based on these, we proposed that the expression of ß-TRCP1 promoted cell proliferation via TNF-dependent NF-κB activation in DLBCL cells.

Silencing of LIMD1 promotes proliferation and reverses cell adhesion-mediated drug resistance in non-Hodgkin's lymphoma.

LIM domains-containing protein 1 (LIMD1) is a tumor suppressor protein downregulated in numerous solid malignancies. However, the functional role of LIMD1 in non-Hodgkin's lymphoma (NHL) remains unclear. In the present study, it was demonstrated that LIMD1 is associated with the proliferation of NHL and cell adhesion mediated-drug resistance (CAM-DR). It was indicated by western blot analysis that LIMD1expression is lower in progressive lymphoma compared with indolent lymphoma. Furthermore, it was indicated that the role of LIMD1 in cell viability and proliferation remains unclear. Finally, the present study demonstrated that LIMD1 serves an important role in CAM-DR by regulating cell cycle progression. Silencing of LIMD1 may reverse CAM-DR in NHL. Therefore, the findings of the present study suggested that LIMD1 may be a potential therapeutic target for patients with NHL.

Elucidating the expression and function of Numbl during cell adhesion-mediated drug resistance (CAM-DR) in multiple myeloma (MM).

BACKGROUND: Cell adhesion-mediated drug resistance (CAM-DR) is a major clinical problem that prevents successful treatment of multiple myeloma (MM). In particular, the expression levels of integrin ß1 and its sub-cellular distribution (internalization and trafficking) are strongly associated with CAM-DR development. METHODS: Development of an adhesion model of established MM cell lines and detection of Numbl and Integrinß1 expression by Western Blot analysis. The interaction between Numbl and Integrinß1 was assessed by a co-immunoprecipitation (CO-IP) method. Calcein AM assay was performed to investigate the levels of cell adhesion. Finally, the extent of CAM-DR in myeloma cells was measured using cell viability assay and flow cytometry analysis. RESULTS: Our preliminary date suggest that Numbl is differentially expressed in a cell adhesion model of MM cell lines. In addition to binding to the phosphotyrosine-binding (PTB) domain, the carboxyl terminal of Numbl can also interact with integrin ß1 to regulate the cell cycle by activating the pro-survival PI3K/AKT signaling pathway. This study intends to verify and elucidate the interaction between Numbl and integrin ß1 and its functional outcome on CAM-DR. We have designed and developed a CAM-DR model using MM cells coated with either fibronectin or bone marrow stromal cells. We assessed whether Numbl influences cell-cycle progression and whether it, in turn, contributes to activation of PI3K/AKT signal pathway through the adjustment of its carboxyl end. Finally, we showed that the interaction of Numbl with integrin ß1 promotes the formation of CAM-DR in MM cells. CONCLUSIONS: Our findings elucidated the specific molecular mechanisms of CAM-DR induction and confirmed that Numbl is crucial for the development of CAM-DR in MM cells.

The genetic architecture of shoot-root covariation during seedling emergence of a desert tree, Populus euphratica.

The coordination of shoots and roots is critical for plants to adapt to changing environments by fine-tuning energy production in leaves and the availability of water and nutrients from roots. To understand the genetic architecture of how these two organs covary during developmental ontogeny, we conducted a mapping experiment using Euphrates poplar (Populus euphratica), a so-called hero tree able to grow in the desert. We geminated intraspecific F1 seeds of Euphrates Poplar individually in a tube to obtain a total of 370 seedlings, whose shoot and taproot lengths were measured repeatedly during the early stage of growth. By fitting a growth equation, we estimated asymptotic growth, relative growth rate, the timing of inflection point and duration of linear growth for both shoot and taproot growth. Treating these heterochronic parameters as phenotypes, a univariate mapping model detected 19 heterochronic quantitative trait loci (hQTLs), of which 15 mediate the forms of shoot growth and four mediate taproot growth. A bivariate mapping model identified 11 pleiotropic hQTLs that determine the covariation of shoot and taproot growth. Most QTLs detected reside within the region of candidate genes with various functions, thus confirming their roles in the biochemical processes underlying plant growth.

Expression of far upstream element binding protein 1 in B­cell non­Hodgkin lymphoma is correlated with tumor growth and cell­adhesion mediated drug resistance.

Cell adhesion­mediated drug resistance (CAM­DR) remains a major obstacle to the effectiveness of chemotherapeutic treatment of lymphoma. Far upstream element binding protein 1 (FBP1) is a multifunctional protein that is highly expressed in proliferating cells of several solid neoplasms; however, its expression and biological function in B­cell lymphoma is largely unknown. FBP1 expression in both reactive lymphoid tissues and several B­cell lymphomas, including follicular lymphoma and diffuse large B­cell lymphoma were detected by immunohistochemistry analysis. FBP1 expression in B­cell lymphoma was also associated with poor survival outcomes. Functionally, small interfering RNA­mediated silencing of FBP1 was able to inhibit the proliferation of B­cell lymphoma cells, resulting in G0/G1 phase cell cycle arrest. Furthermore, results of a cell adhesion assay demonstrated that adhesion to fibronectin or bone marrow stromal cells induced FBP1 expression, which in turn facilitated cell adhesion. Finally, FBP1 knockdown reversed CAM­DR. These findings support a role for FBP1 in non­Hodgkin lymphoma cell proliferation, adhesion and drug resistance, and may lead to the generation of a novel therapeutic approach targeting this molecule.

Expression of vaccinia-related kinase 1 (VRK1) accelerates cell proliferation but overcomes cell adhesion mediated drug resistance (CAM-DR) in multiple myeloma.

OBJECTIVE: Vaccinia-related kinase 1 (VRK1) has been reported to participate in the development of a variety of tumors. However, the role of VRK1 in multiple myeloma (MM) has not been investigated. The present study was undertaken to determine the expression and biologic function of VRK1 in human MM. METHODS: First, we constructed a model of cell adhesion in MM, the mRNA and protein level of VRK1 in suspension and adhesion model was analyzed by RT-PCR and western blot. Then, flow cytometry assay and western blot were used to investigate the mechanism of VRK1 in the proliferation of MM cells. In vitro, following using shRNA interfering VRK1 expression, we performed adhesion assay and cell viability assay to determine the effect of VRK1 on adhesive rate and drug sensitivity. RESULTS: VRK1 was lowly expressed in adherent MM cells and highly expressed in suspended cells. In addition, VRK1 was positively correlated with the proliferation of MM cells by regulating the expression of cell cycle-related protein, such as cyclinD1, CDK2 and p27kip1. Furthermore, VRK1 could reverse cell adhesion mediated drug resistance (CAM-DR) by down-regulating the ability of cell adhesion. CONCLUSION AND DISCUSSION: Our data supports a role for VRK1 in MM cell proliferation, adhesion, and drug resistance, and it may pave the way for a novel therapeutic approach for CAM-DR in MM.