Background Transcriptional regulators are seminal players in the onset and progression of prostate cancer. However, clarification of their underlying regulatory circuits and mechanisms demands considerable effort. Methods Integrated analyses were performed on genomic, transcriptomic, and clinicopathological profiles of primary prostate cancer and transcription factor-binding profiles, which included estimating transcription factor activity, identifying transcription factors of prognostic values, and discovering cis- and trans-regulations by long noncoding RNAs. Interactions between transcription factors and long noncoding RNAs were validated by RNA immunoprecipitation quantitative PCR. RNA interference assays were performed to explore roles of the selected transcription regulators. Findings Sixteen transcription factors, namely, ETS1, ARID4B, KLF12, GMEB1, HBP1, MXI1, MYC, MAX, PGR, BCL11A, AR, KLF4, SRF, HIF1A, EHF, and ATOH1, were jointly identified as a prognostic signature. Candidate long noncoding RNAs interplaying with the prognostic signature constituent transcription factors were further discovered. Their interactions were randomly checked, and many of them were experimentally proved. Transcription regulation by MYC and its long noncoding RNA partner AL590617.2 was further validated on their candidate targets. Moreover, the regulatory network governed by the transcription factors and their interacting long noncoding RNA partners is illustrated and stored in our LNCTRN database (https://navy.shinyapps.io/lnctrn). Interpretation The prognostic signature constituent transcription factors and their interacting long noncoding RNAs may represent promising biomarkers and/or therapeutic targets for prostate cancer. Furthermore, the computational framework proposed in the present study can be utilized to explore critical transcriptional regulators in other types of cancer. Funding This work was supported by National Natural Science Foundation of China and Fudan University.

Chemo-resistance is considered a key problem in triple negative breast cancer (TNBC) chemotherapy and as such, an urgent need exists to identify its exact mechanisms. Inhibitor of DNA binding factor 4 (ID4) was reported to play diverse roles in different breast cancer molecular phenotypes. In addition, ID4 was associated with mammary carcinoma drug resistance however its functions and contributions remain insufficiently defined. The expression of ID4 in MCF-7, MCF-7/Adr and MDA-MB-231 breast cancer cell lines and patients' tissues were detected by RT-PCR, western blot and immunohistochemistry. Furthermore, TCGA database was applied to confirm these results. Edu and CCK8 assay were performed to detect the proliferation and drug resistance in breast cancer cell lines. Transwell and scratch migration assay were used to detected metastasis. Western blot, TCGA database, Immunoprecipitation (IP), Chromatin Immunoprecipitation (ChIP) and Luciferase reporter assay were used to investigate the tumor promotion mechanisms of ID4. In this study, we report that the expression levels of ID4 appeared to correlate with breast cancers subtype differentiation biomarkers (including ER, PR) and chemo-resistance related proteins (including MRP1, ABCG2, P-gp). Down-regulation of ID4 in MCF-7/Adr and MDA-MB-231 breast cancer cell lines significantly suppressed cell proliferation and invasion, however enhanced Adriamycin sensitivity. We further demonstrated that the oncogenic and chemo-resistant effects of ID4 could be mediated by binding to CBF1 promoter region though combination with MyoD1, and then the downstream target MRP1 could be activated. We reveal for the first time that ID4 performs its function via a CBF1-MRP1 signaling axis, and this finding provides a novel perspective to find potential therapeutic targets for breast cancer chemotherapy.

The AR signaling pathway plays an important role in initiation and progression of many hormone-related cancers including prostate, bladder, kidney, lung, and breast cancer. However, the potential roles of androgen-responsive long noncoding RNAs (lncRNAs) in hormone-related cancers remained unclear. In the present study, we identified 469 novel androgen-responsive lncRNAs using microarray data. After validating the accuracy of the array data, we constructed a transcriptional network which contained more than 30 transcriptional factors using ChIP-seq data to explore upstream regulators of androgen-responsive lncRNAs. Next, we conducted bioinformatics analysis to identify lncRNA-miRNA-mRNA regulatory network. To explore the potential roles of androgen-responsive lncRNAs in hormone-related cancers, we performed coexpression network and PPI network analyses using TCGA data. GO and KEGG analyses showed these lncRNAs were mainly involved in regulating signal transduction, transcription, development, cell adhesion, immune response, cell differentiation, and MAPK signaling pathway. We also highlight the prognostic value of HPN-AS1, TPTEP1, and LINC00623 in cancer outcomes. Our results suggest that androgen-responsive lncRNAs played important roles in regulating hormone-related cancer progression and could be novel molecular biomarkers.

Introduction Prostate cancer (PCa) is the most commonly diagnosed cancer and the third leading cause of cancer-related death in males in the United States. Despite the initial efficacy of androgen deprivation therapy in prostate cancer (PCa) patients, most patients progress to castration-resistant prostate cancer. However, the mechanisms underlying the androgen-independent progression of PCa remain largely unknown. Methods In this study, we established a PCa cell line (LNCaP-AI) by maintaining LNCaP cells under androgen-depleted conditions. To explore the cellular and molecular mechanisms of androgen-independent growth of PCa, we analyzed the gene expression patterns in androgen-independent prostate cancer (AIPC) compared with that in androgen-dependent prostate cancer (ADPC). KEGG pathway analysis revealed that Wnt signaling pathways were activated after androgen deprivation therapy (ADT). In vitro experiments showed that the inhibition of Wnt pathway reduced AIPC cell growth by inhibiting cell cycle progression and promoting apoptosis. Furthermore, WNT5A, LEF1 were identified as direct targets of AR by chromatin immunoprecipitation (ChIP) assay and public ChIP-seq datasets analysis. Results In the present study, we found a regulatory mechanism through which crosstalk between androgen receptor (AR) and Wnt signals promoted androgen-independent conversion of PCa. The Wnt pathway was inhibited by androgen in androgen-dependent prostate cancer cells, but this blocking effect was not elicited in androgen-independent prostate cancer (AIPC) cells. Moreover, Wnt pathway genes WNT5A and LEF1 were directly downregulated by AR. In vitro experiments showed that inhibition of the Wnt pathways repressed AIPC cell growth by inhibiting cell cycle progression and promoting apoptosis. We found that WNT5A and LEF1 were downregulated in low-grade PCa but upregulated in metastatic PCa. Conclusion In summary, we revealed that crosstalk between AR and Wnt signaling pathways promotes androgen-independent growth of PCa, which may provide novel therapeutic opportunities for castration-resistant prostate cancer.

BACKGROUND:Prostate cancer (PCa) is one of the most common cancers in males in China. Long noncoding RNAs (lncRNAs) reportedly play crucial roles in human cancer progression in many studies. However, the molecular mechanisms underlying PCa progression remain unclear.MATERIALS AND METHODS:We investigated the lncRNA transcriptome using publicly available RNA-sequencing data to identify prostate-specific lncRNAs. Then, the chromatin immunoprecipitation (ChIP) assay identified lncRNA with a direct binding to androgen receptor (AR), hereafter denoted as PSLNR. Quantitative real-time polymerase chain reaction analysis and Western blot analysis were performed to detect the expression of p53 signaling-related genes after overexpression PSLNR. The effects of overexpression of PSLNR on cell proliferation, cell cycle, and cell apoptosis were assessed by using CCK-8 and flow cytometric analysis. We then detected the expression of PSLNR in tissues.RESULT:We reported a novel androgen-reduced prostate-specific lncRNA, PSLNR, that inhibited PCa progression via the p53-dependent pathway. By analyzing the NOCODE data set, we reported that PSLNR was specifically expressed in the prostate, suggesting the potential of PSLNR as a biomarker for PCa treatment. The AR pathway was also confirmed to be an upstream regulation signaling pathway of PSLNR by transcriptionally regulating its expression in androgen-dependent PCa cells. PSLNR also significantly inhibited PCa proliferation by inducing cell apoptosis in a p53-dependent manner. Thus, PSLNR may be a candidate diagnosis and therapeutic target for PCa.CONCLUSIONS:Our study revealed for the first time a novel androgen-reduced prostate-specific lncRNA, PSLNR, which inhibited PCa progression via the p53-dependent pathway, suggesting that PSLNR may be a candidate diagnosis and therapeutic target for PCa.

Glioma is one of the most aggressive malignant brain tumors which is characterized with highly infiltrative growth and poor prognosis. NKAP (NF-κB activating protein) is a widely expressed 415-amino acid nuclear protein that is overexpressed by gliomas, but its function in glioma was still unknown. CCK8 and EDU assay was used to examine the cell viability in vitro, and the xenograft models in nude mice were established to explore the roles of NAKP in vivo. The expressions of NKAP, Notch1 and SDF-1 were analyzed by immunofluorescence analysis. The expression of NKAP and Notch1 in glioma and normal human brain samples were analyzed by immunohistochemical analysis. In addition, CHIP, Gene chip, western blot, flow cytometry, immunofluorescence, ELISA and luciferase assay were used to investigate the internal connection between NKAP and Notch1. Here we showed that overexpression of NKAP in gliomas could promote tumor growth by contributing to a Notch1-dependent immune-suppressive tumor microenvironment. Downregulation of NKAP in gliomas had abrogated tumor growth and invasion in vitro and in vivo. Interestingly, compared to the control group, inhibiting NKAP set up obstacles to tumor-associated macrophage (TAM) polarization and recruitment by decreasing the secretion of SDF-1 and M-CSF. To identify the potential mechanisms involved, we performed RNA sequencing analysis and found that Notch1 appeared to positively correlate with the expression of NKAP. Furthermore, we proved that NKAP performed its function via directly binding to Notch1 promoter and trans-activating it. Notch1 inhibition could alleviate NKAP’s gliomagenesis effects. these observations suggest that NKAP promotes glioma growth by TAM chemoattraction through upregulation of Notch1 and this finding introduces the potential utility of NKAP inhibitors for glioma therapy.

BackgroundProstate cancer (PCa) is a leading cause of death in males all over the world; besides, the diagnosis and therapy of it are still challenging. Researchers have revealed that long non‐coding RNAs (lncRNAs) play important roles in the genesis and progression of human cancers, including PCa.MethodsBioinformatics analysis and Kaplan‐Meier survival analysis were utilized to confirm TMPO‐AS1 as a diagnostic and prognostic marker. The TMPO‐AS1 levels in both patient tissues and PCa cell lines were determined by qRT‐PCR analysis. Moreover, the chromatin immunoprecipitation (ChIP) assay identified that TMPO‐AS1 was a direct target of AR. The effect of overexpression or knockdown of TMPO‐AS1 on cell proliferation, migration, cell cycle, and cell apoptosis was assessed by using CCK‐8, transwell assays, and flow cytometric analysis, respectively.ResultsBased on primary screening, we found that TMPO‐AS1 could be a useful diagnostic and prognostic marker for PCa, whose expression was upregulated in PCa samples and associated with poorer prognosis. Bioinformatics predictions revealed TMPO‐AS1 was associated with a series of biological processes involved in PCa progression. In PCa cells, TMPO‐AS1 was predominantly localized in the cytoplasm and directly down‐regulated by AR. Gain/loss‐of‐function assays showed TMPO‐AS1 overexpression increased cell proliferation by promoting cell cycle progression and promoted migration, but reduced apoptosis of PCa cells. In addition, TMPO‐AS1 may be a diagnostic and prognostic marker in multiple cancer types.ConclusionsAR‐regulated lncRNA TMPO‐AS1 functioned as an oncogenic lncRNA in PCa, and may be a potential diagnostic and prognostic biomarker to be used as a therapeutic target for PCa.

BACKGROUND:Cancer cells maintain energy metabolism mainly by glycolysis, even under sufficient oxygen conditions. It gives cancer cells better growth advantages under complicated internal environment. KPNA2 is a novel oncogene that has received much attention in recent years, but the exact mechanisms of KPNA2 in tumorigenesis and progression are largely unknown. Especially its potential roles in the metabolic transformation of tumors still remain to be explored.METHODS:The expressions of KPNA2 in glioblastoma and normal human brain samples were analyzed by immunohistochemical analysis. The activities of key enzymes in glycolysis, the production of lactate acid and glucose uptake were investigated by colorimetry. GLUT-1 expression was measured by flow cytometry. CCK8 was used to examine the cell viability in vitro, and the xenograft models in nude mice were established to explore the roles of KPNA2 in vivo. In addition, Co-IP, subcellular fractionation, western blot, immunofluorescence and luciferase assay were used to investigate the internal connection between KPNA2, c-myc and E2F1.RESULTS:In the present study, we found that KPNA2 was highly expressed in the glioma compared to the normal brain tissues. Level of KPNA2 was an independent predictor of prognosis in the glioma patients. Knockdown of KPNA2 in the glioblastoma cell lines U87 and U251 decreased deoxyglucose uptake, activities of the key glycolytic enzymes and lactate production. The level of oxidative phosphorylation (OXPHOS) was moderately decreased. Additioanlly, tumor proliferation and invasiveness were concomitantly downregulated. We have identified c-myc as a potential mediator of KPNA2. Aberrant expression of KPNA2 significantly changed the subcellular distribution of c-myc as well as its expression level. E2F1, another key cargo protein of KPNA2, was further identified to play a potential role in regulating the transcription of c-myc by KPNA2.CONCLUSIONS:Our findings suggested that KPNA2, a potential tumor oncogene, performs its function in part via regulating cellular metabolism through c-myc signaling axis. It would provide a possible explanation for Warburg effect and thus offer a new perspective to the roles of KPNA2 in gliomagenesis.

Developing magnetic resonance imaging (MRI) contrast agents with high relaxivity and specificity was essential to increase MRI diagnostic sensitivity and accuracy. In this study, the MRI contrast agent, vascular endothelial growth factor receptor (VEGFR)-targeted poly (l-lysine) (PLL)-diethylene triamine pentacetate acid (DTPA)-gadolinium (Gd) (VEGFR-targeted PLL-DTPA-Gd, VPDG), was designed and prepared to enhance the MRI diagnosis capacity of tumor. Biotin-PLL-DTPA-Gd was synthesized first, then, VEGFR antibody was linked to biotin-PLL-DTPA-Gd using biotin-avidin reaction. In vitro cytotoxicity study results showed that VPDG had low toxicity to MCF-7 cells and HepG2 cells at experimental concentrations. In cell uptake experiments, VPDG could significantly increase the internalization rates (61.75%±5.22%) in VEGFR-positive HepG2 cells compared to PLL-DTPA-Gd (PDG) (25.16%±4.71%, P<0.05). In MRI studies in vitro, significantly higher T1 relaxivity (14.184 mM-1 s-1) was observed compared to Magnevist® (4.9 mM-1 s-1; P<0.01). Furthermore, in vivo MRI study results showed that VPDG could significantly enhance the tumor signal intensity and prolong the diagnostic time (from <1 h to 2.5 h). These results indicated that macromolecular VPDG was a promising MRI contrast agent and held great potential for molecular diagnosis of tumor.

Acute lymphoblastic leukemia (ALL) is an aggressive hematological tumor resulting from the malignant transformation of lymphoid progenitors. Thiopurine is a widely used drug in the maintaining treatment of ALL. After a period of chemotherapy, 20% of pediatric patients and over 50% of adult patients will relapse. To investigate the mechanisms of drug resistance in vitro, we established the thiopurine resistant cell lines Reh-6MPR (6-MP Resistant cell) and Reh-6TGR (6-TG Resistant cell) by stepwise selection of the ALL cell line Reh. Cell viability assay revealed that 6MPR and 6TGR cells were almost 1000-fold more resistant to thiopurine comparing with the control Reh cells, and thiopurine conversion was significantly impaired in the resistant cells. Mechanistically, a same novel hypoxanthine phosphoribosyl transferase 1 (HPRT1) mutation c.495_496insA (p.V165fs) was found by whole exome sequencing in both resistant cells. The HPRT1 mutation dramaticly decreased the production of [13C5,15N4]-IMP from [13C5,15N4]-hypoxanthine (HX), showed a loss-of-funciton mechanism. Notably, re-expression the wildtype HPRT1 in Reh-6MPR cell can reverse the drug resistance and thiopurine conversion in Reh-6MPR cells. These results highlight the importance of HPRT1's activity in thiopurine resistance.

Uridine diphosphate glucuronosyltransferase 1A (UGT1A1), which affects irinotecan metabolism, has been associated with severe adverse reactions in patients with cancer treated with irinotecan. However, neither large-scale analysis of the distribution of UGT1A1 polymorphisms, nor standardized assessment of how UGT1A1 polymorphisms affect irinotecan treatment has been performed in China. The aim of the present study was to investigate the distribution of UGT1A1 polymorphisms (*28 and *6) in 2,093 Chinese patients with cancer who were treated with irinotecan from more than 15 hospitals in Shandong, to examine how the coexistence of UGT1A1*6 and UGT1A1*28 alleles may be able to predict toxicities induced by irinotecan in 105 of the patients, and to search for other relevant risk factors. The distribution of the genotypes was as follows: TA6/TA6 (1,601, 76.5%), TA6/TA7 (463, 22.1%) and TA7/TA7 (29, 1.4%) for UGT1A1*28 (n=2,093); and G/G (286, 66.4%), G/A (124, 28.8%) and A/A (21, 4.9%) for UGT1A1*6 (n=431). The most frequent severe hematological toxicity was neutropenia, and the predominant non-hematological toxicities were diarrhea and cholinergic syndrome. In toxicity comparisons, grade 3-4 leukopenia and neutropenia were significantly higher in TA6/TA7 compared with TA6/TA6 (P<0.05). The UGT1A1*6 polymorphism was associated with a higher risk of severe diarrhea and total adverse drug reactions (P<0.05). Logistic regression showed that the UGT1A1*6 genotype was an independent predictor of severe diarrhea. These findings suggested that the UGT1A1*28 and UGT1A1*6 genotypes may be associated with irinotecan-induced severe toxicity, and clarified the clinical importance of UGT1A1 polymorphisms, particularly UGT1A1*6, regarding irinotecan therapy in Chinese patients.

Prostate cancer (PCa) is a leading cause of cancer-related deaths among males worldwide. However, the molecular mechanisms underlying the progression of PCa remain unclear. Despite several reported miRNAs in prostate cancer, these reports lacked system-level identification of differentially expressed miRNAs in large sample size. Moreover, it's still largely unknown how miRNAs result in tumorigenesis and progression of PCa. Therefore, by analyzing three public databases, we identified 16 upregulated miRNAs and 13 downregulated miRNAs, and validated miR-19a was one of the most upregulated miRNAs using qRT-PCR. The dual-luciferase reporter assays indicated VPS37A was a potential target of miR-19a. Functional assays revealed miR-19a served as an oncogene by inhibiting VPS37A. Notably, a significant inverse correlation of miR-19a and VPS37A expression was observed in PCa specimens. Moreover, miR-19a-high and VPS37A-low phenotypes were associated with poor prognosis with biochemical recurrence-free probability. In this study, we confirmed the oncogenic role of miR-19a via targeting VPS37A in PCa, identifying miR-19a and VPS37A as diagnosis and therapeutic biomarkers for PCa.

Subclinical hypothyroidism (SCH) is highly prevalent in the general population and is associated with potential deleterious effects. Although developing T cells express thyroid-stimulating hormone receptor (TSH-R), the changes of T cell development in thymus in SCH have not been fully clarified. SCH mouse model, which is characterized by elevated serum TSH but similar thyroid hormone levels, was used to study the role of TSH in T cell development. Thymus weight of SCH mice increased 18% compared with controls. Importantly, the frequencies of CD4+ and CD8+ single-positive (SP) thymocytes increased 38% and 44%, respectively. We demonstrated that TSH protected thymocytes from apoptosis as evidenced by a significant decrease of Annexin V-positive thymocytes in SCH mice. Further analysis showed that extracellular-regulated kinases (ERK) 1/2 in thymus were activated in SCH mice. With analysis of T cell receptor excision circles (TREC), we found that TSH increased recent thymic emigrants (RTE) in spleen tissue in SCH mice. Thus, these results suggest that TSH promoted T cell development and enhanced the thymic recent output in SCH mice, possibly by suppression of apoptosis of thymocytes, indicating that modification of the ERK signalling pathways.

Prostate cancer (PCa) becomes a leading cause of death in males nowadays. Recent reports showed that androgen-responsive long non-coding RNAs played important roles in tumorigenesis and progression of PCa. In this study, we focused on a special transcript of GAS5 (ENST00000456293.5, GAS5-007), which was reported as a tumor suppressor. Here, we demonstrated GAS5-007 was reduced by androgen treatment and inhibited by AR. Next, we explored the expression level of GAS, finding the expression of it in PCa tissue was higher than normal tissue in both public databases and human tissue samples. Functional analysis of GAS5 showed it was related to regulating translational elongation, protein biosynthesis, and transcription. Moreover, we observed GAS5-007 knockdown inhibited the proliferation, cell cycle and promoted cell apoptosis of PCa. We also constructed a GAS5-miRNA network to explain the different roles of different GAS5 transcripts in PCa. This study provides novel insights to identify potential diagnostic biomarker and therapy target for prostate cancer in clinical treatment.

Purpose: To investigate the value of the muscle-to-bone ratio (MBR), which is the ratio between the maximum pronator quadratus thickness (mPQT) and the distal radial thickness (DRT) at the same level, in comparison with mPQT in the diagnosis of undisplaced fractures in distal forearm (FDF) on radiographs.Material and methods: This study was conducted with 210 wrists of 210 volunteers (79 male, 131 female) and 106 wrists of 106 patients with acute undisplaced FDF (53 male, 53 female). The mPQT was measured on lateral radiographs, and the MBR was calculated for each wrist.Results: The mean mPQT (7.37 + 1.99 mm) and MBR (0.55 + 0.15) in the fracture group were significantly larger than those (4.70 + 1.42 mm and 0.31 + 0.09) in the control group respectively (all P< 0.05). Sexual differences of mPQT were found in both control and fracture groups (all P< 0.05). There were no gender differences of MBR in either control or fracture group (all P> 0.05). ROC analysis revealed that the discriminating efficacy of MBR was significantly superior to that of mPQT (P< 0.01). The most optimal diagnostic discrimination was obtained by a MBR cut-off value of 0.4.Conclusions: The MBR can be used as a new index for the diagnosis of undisplaced FDF, as well as a complementary means to detect occult fractures. If the MBR is larger than 0.4 in a patient with suspected or occult FDF, a further MRI examination will be justifiably needed. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

Lymphatic metastasis is a primary cause of gastric cancer-related death, yet factors governing tumor cell lymphatic metastasis have not been fully elucidated. Little is known about the contributions of long noncoding RNAs (lncRNAs) to lymphatic metastasis in gastric cancer. Differentially expressional lncRNAs between metastatic lymph node tissues and normal lymph node tissues were identified and validated by microarray and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Our results found that the expression level of C21orF96 was over-expressed in positive lymph node tissues and gastric cancer tissues. We evaluated the altered expressions of C21orF96 in gastric cancer tissues comparing to adjacent normal specimens, and their association with clinicopathological factors. We showed that the expression levels of C21orF96 were associated with gross appearance, lymphatic metastasis and distal metastasis. The effect of C21orF96 was assessed by over-expressing the lncRNA. We also found that C21orF96 promoted the tubular formation, migration and invasion. Together, our results suggest that C21orF96 is an oncogenic lncRNA that promotes tumor progression and plays a pivotal role in the development of gastric cancer.

Purpose To provide an assessment by meta-analysis of the relationship between the expression variations of 5-fluorouracil metabolic enzymes and clinical outcomes in patients with gastric cancer treated with S-1. Method Databases were searched electronically from inception to April 19th, 2015. Studies in gastric cancer patients treated with S-1 investigating the expression variations of 5-fluorouracil metabolic enzymes were included after having been identified systematically. Pooled odds ratios (OR) for the objective response rate (ORR) and median survival ratio were calculated using the Review Manager 5.3 and Stata 12.0 software separately. Results A total of 555 patients in 10 studies met our inclusion criteria. There was a significant difference in ORR between patients with high/+ and low/- expression of orotate phosphoribosyl transferase (OPRT) (OR = 8.06; 95% CI, 4.06-16.02; p<0.001) and dihydropyrimidine dehydrogenase (DPD) (OR = 1.95; 95% CI, 1.21-3.13; p = 0.006). There was no significant difference in ORR between different expression levels of thymidylate synthase (TS) and thymidine phosphorylase (TP). Although patients with low/- TS expression, low/- TP expression and high/+ DPD expression showed a trend towards longer survival, no statistical significance was found. The median OS was significantly longer in patients with high/+ expression of OPRT (p = 0.076). Conclusions OPRT and DPD expression can be treated as a potential predictive biomarker for S-1 response in gastric cancer patients. Further investigation is warranted.

The contribution of long noncoding RNAs (lncRNAs) to metastasis of gastric cancer remains largely unknown. We used microarray analysis to identify lncRNAs differentially expressed between normal gastric tissues and gastric cancer tissues and validated these differences in quantitative real-time (qRT)-PCR experiments. The expression levels of lncRNA olfactory receptor, family 3, subfamily A, member 4 (OR3A4) were significantly associated with lymphatic metastasis, the depth of cancer invasion, and distal metastasis in 130 paired gastric cancer tissues. The effects of OR3A4 were assessed by overexpressing and silencing OR3A4 in gastric cancer cells. OR3A4 promoted cancer cell growth, angiogenesis, metastasis, and tumorigenesis in vitro and in vivo. Global microarray analysis combined with RT-PCR, RNA immunoprecipitation, and RNA pull-down analyses after OR3A4 transfection demonstrated that OR3A4 influenced biologic functions in gastric cancer cells via regulating the activation of PDLIM2, MACC1, NTN4, and GNB2L1. Our results reveal OR3A4 as an oncogenic lncRNA that promotes tumor progression, Therefore, lncRNAs might function as key regulatory hubs in gastric cancer progression.

The Schatzker classification of tibial plateau fractures is widely accepted. Type IV fractures are medial tibial plateau fractures that are either split off as a wedge fragment or depressed and comminuted. Posterior articular surface depression in Schatzker type IV tibial plateau fractures can be seen as a unique variant that increases the difficulty of reduction of the articular surface. Its morphologic characteristics have not been fully studied, and the incidence is sometimes underestimated. The goal of this study was to evaluate the morphologic characteristics of posterior articular depression in Schatzker type IV fractures based on computed tomography measurements. From January 2009 to December 2011, the medical records, including digital radiologic data, of all patients treated for tibial plateau fracture at the authors' institution were retrospectively analyzed. Articular surface depression deeper than 5 mm was the criterion for study inclusion. The depression depth, precise location of the articular depression center, surface area percentage, and distance of the fracture gap to the depression center were calculated. One hundred fifteen cases of Schatzker type IV fracture were retrieved, and a total of 47.83% (55 of 115) cases had posterior articular surface depression. The average depth of the depressed articular surface was 12.41 mm, the surface area percentage was 20.15% of the entire tibial plateau, and the gap distance from the medial direction was 41.40 mm, 2.8 times longer than that from the posterior direction, which was 14.91 mm. Posterior articular surface depression occurs in nearly half of Schatzker type IV fractures, and the posterior approach provides more direct access to the depression than the medial approach.