Hepatocellular carcinoma (HCC) is a primary cause of mortality from cancer, necessitating novel insights into its molecular underpinnings. Recent evidence points to the significant roles of lncRNAs in HCC progression, among which CTB-31O20.2 has emerged as a potentially crucial player. This study utilized RNA sequencing to identify differentially expressed lncRNAs in HCC tissues, focusing on CTB-31O20.2. We employed RT-qPCR, Western blotting, and dual-luciferase reporter assays to evaluate the expression patterns of CTB-31O20.2 in HCC cells and its interactions with miR-139-5p and Rho-associated coiled-coil containing protein kinase1 (ROCK1). In vivo effects were analyzed using a xenograft mouse model. CTB-31O20.2 was significantly upregulated in HCC tissues and cell lines. Silencing CTB-31O20.2 in Hep3B and HepG2 cells reduced malignancy, evidenced by decreased viability, colony formation, and invasion, and increased apoptosis. These cellular behaviors were associated with alterations in apoptosis-related proteins and epithelial-mesenchymal transition (EMT) markers. CTB-31O20.2 was shown to interact with miR-139-5p, and its silencing upregulated miR-139-5p, leading to reduced ROCK1 expression. Conversely, miR-139-5p inhibition reversed the anti-tumor effects of CTB-31O20.2 silencing. Overexpression of ROCK1 negated the inhibitory effects on HCC cell malignancy induced by CTB-31O20.2 depletion. In vivo, CTB-31O20.2 silencing significantly reduced tumor growth in a xenograft model. Our findings reveal that CTB-31O20.2 contributes to HCC progression by modulating miR-139-5p and ROCK1 expression. These results highlight CTB-31O20.2 as a potential therapeutic target in HCC, providing a new perspective on the mechanisms driving HCC pathogenesis and progression.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. Chemotherapy is the mainstay of treatment for patients with CRC in II-IV stages. Resistance to chemotherapy occurs commonly, which results in treatment failure. Therefore, the identification of novel functional biomarkers is essential for recognizing high-risk patients, predicting recurrence, and developing new therapeutic strategies. Herein, we assessed the roles of KIAA1549 in promoting tumor development and chemoresistance in colorectal cancer. As a result, we found that KIAA1549 expression is up-regulation in CRC. Public databases revealed a progressive up-regulation of KIAA1549 expression from adenomas to carcinomas. Functional characterization uncovered that KIAA1549 promotes tumor malignant phenotypes and boosts the chemoresistance of CRC cells in an ERCC2-dependent manner. Inhibition of KIAA1549 and ERCC2 effectively enhanced the sensitivity to chemotherapeutic drugs oxaliplatin and 5-fluorouracil. Our findings suggest that endogenous KIAA1549 might function as a tumor development-promoting role and trigger chemoresistance in colorectal cancer partly by upregulating DNA repair protein ERCC2. Hence, KIAA1549 could be an effective therapeutic target for CRC and inhibition of KIAA1549 combined with chemotherapy might be a potential therapeutic strategy in the future.

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, and tumor recurrence and metastasis are major factors that contribute to the poor outcome of patients with HCC. Long noncoding RNAs (lncRNAs) are known to regulate different tumorigenic processes, and a growing body of evidence indicates that Hippo kinase signaling is inactivated in many cancers. However, the upstream lncRNA regulators of Hippo kinase signaling in HCC are poorly understood. Methods Using a lncRNA microarray, we identified a novel lncRNA, uc.134, whose expression was significantly decreased in the highly aggressive HCC cell line HCCLM3 compared with MHCC97L cells. Furthermore, we evaluated uc.134 expression in clinical samples using in situ hybridization (ISH) and quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The full-length transcript of uc.134 was confirmed using rapid amplification of cDNA ends (RACE) analyses. To investigate the biological function of uc.134, we performed gain-of-function and loss-of-function studies both in vitro and in vivo. The underlying mechanisms of uc.134 in HCC were investigated using RNA pulldown, RNA immunoprecipitation, ubiquitination assays, Western blotting, mRNA microarray analyses, and qRT-PCR analyses. Results The ISH assay revealed that uc.134 expression was significantly decreased in 170 paraffin-embedded samples from patients with HCC compared with adjacent tissues and uc.134 expression directly correlated with patient prognosis. Furthermore, we defined a 1867-bp full-length transcript of uc.134 using 5′- and 3′-RACE analysis. The overexpression of uc.134 inhibited HCC cell proliferation, invasion, and metastasis in vitro and in vivo, whereas the knockdown of uc.134 produced the opposite results. Furthermore, we confirmed that uc.134 (1408–1867 nt) binds to CUL4A (592–759 aa region) and inhibits its nuclear export. Moreover, we demonstrated that uc.134 inhibits the CUL4A-mediated ubiquitination of LATS1 and increases YAPS127 phosphorylation to silence the target genes of YAP. Finally, a positive correlation between uc.134, LATS1, and pYAPS127 was confirmed in 90 paraffin-embedded samples by ISH and immunohistochemical staining. Conclusions Our study identifies that a novel lncRNA, uc.134, represses hepatocellular carcinoma progression by inhibiting the CUL4A-mediated ubiquitination of LATS1 and increasing YAPS127 phosphorylation. The use of this lncRNA may offer a promising treatment approach by inhibiting YAP and activating Hippo kinase signaling.

Radiation enteritis (RE) is a common complication in cancer patients receiving radiotherapy. Although studies have shown the changes of this disease at clinical, pathological and other levels, the dynamic characteristics of local microbiome and metabolomics are hitherto unknown. We aimed to examine the multi-omics features of the gut microecosystem, determining the functional correlation between microbiome and lipid metabolites during RE activity. By delivering single high-dose irradiation, a RE mouse model was established. High-throughput 16S rDNA sequencing and global lipidomics analysis were performed to examine microbial and lipidomic profile changes in the gut microecosystem. Spearman correlation analysis was used to determine the functional correlation between bacteria and metabolites. Clinical samples were collected to validate the above observations. During RE activity, the intestinal inflammation of the mice was confirmed by typical signs, symptoms, imaging findings and pathological evidences. 16S datasets revealed that localized irradiation dramatically altered the gut microbial composition, resulting in a decrease ratio of Bacteroidetes to Firmicutes. Lipidomics analysis indicated the remarkable lipidomic profile changes in enteric epithelial barrier, determining that glycerophospholipids metabolism was correlated to RE progression with the highest relevance. Spearman correlation analysis identified that five bacteria-metabolite pairs showed the most significant functional correlation in RE, including Alistipes-PC(36:0e), Bacteroides-DG(18:0/20:4), Dubosiella-PC(35:2), Eggerthellaceae-PC(35:6), and Escherichia-Shigella-TG(18:2/18:2/20:4). These observations were partly confirmed in human specimens. Our study provided a comprehensive description of microbiota dysbiosis and lipid metabolic disorders in RE, suggesting strategies to change local microecosystem to relieve radiation injury and maintain homeostasis.

Upregulation of histone methyltransferase SET domain bifurcated 1 (SETDB1) is associated with poor prognosis in cancer patients. However, the mechanism of oncogenicity of SETDB1 in cancer is hitherto unknown. Here, we show that SETDB1 is upregulated in human colorectal cancer (CRC) where its level correlates with poor clinical outcome. Ectopic SETDB1 promotes CRC cell proliferation, whereas SETDB1 attenuation inhibits this process. Flow cytometry reveals that SETDB1 promotes proliferation by driving the CRC cell cycle from G0/G1 phase to S phase. Mechanistically, SETDB1 binds directly to the STAT1 promoter region resulting in increased STAT1 expression. Functional characterization reveals that STAT1-CCND1/CDK6 axis is a downstream effector of SETDB1-mediated CRC cell proliferation. Furthermore, SETDB1 upregulation is sufficient to accelerate in vivo proliferation in xenograft animal model. Taken together, our results provide insight into the upregulation of SETDB1 within CRC and can lead to novel treatment strategies targeting this cell proliferation-promoting gene.

BACKGROUND:SETDB1 is a histone H3K9 methyltransferase, which plays a significant role in the occurrence and progression of tumors. Previous studies have confirmed that T-lymphom invasion and metastasis gene (Tiam1) is a protein associated with the metastasis of hepatocellular carcinoma (HCC); however, we have not yet been successful in elucidating the specific mechanism of HCC.METHODS:Yeast two-hybrid test was conducted to screen proteins that interacted with Tiam1 gene. Glutathione-S-transferase (GST) pull-down and crosslinking-immunoprecipitation (CLIP) assays were performed to determine whether SETDB1 can interact with Tiam1 gene. A series of related experiments were performed to explore role of SETDB1 on cell proliferation, migration, and invasion in HCC. Recovery experiment was performed to investigate the effect of Tiam1 knockdown on cell proliferation and migration, which was caused by SETDB1 overexpression in HCC cells. The expression of SETDB1 was frequently upregulated in HCC tissues and positively correlated with Tiam1.RESULTS:GST pull-down and CLIP assays were performed to elucidate the interaction between SETDB1 and Tiam1. Cell proliferation, migration, and epithelial mesenchymal transformation (EMT) in HCC cells was promoted with the overexpression of SETDB1. Following the knockdown of Tiam1 gene, the effect of SETDB1 on cell proliferation and migration was reversed in HCC cells. The expression of SETDB1 was frequently up-regulated in HCC tissues, and it was positively correlated with Tiam1 gene.CONCLUSIONS:Ours is the first study to prove that SETDB1 promotes the proliferation and migration of cells by forming SETDB1-Tiam1 compounds. We found that SETDB1-Tiam1 compounds were involved in a novel pathway, which regulated epigenetic modification of gene expression in HCC samples.

Zinc finger protein 307 (ZNF307) is a new Kruppel-associated box zinc-finger protein gene and a member of the zinc-finger family of transcriptional factors. Notably, the role of ZNF307 and its underlying mechanisms involved in hepatocarcinogenesis are poorly investigated. In the present study, we found that the expression of ZNF307 was significantly downregulated in hepatocellular carcinoma (HCC) tissues, compared with that in adjacent non-tumor tissues. In vitro studies further demonstrated that ectopic expression of ZNF307 in HCC cell lines Bel7402 and HCCLM3 significantly reduced cell proliferation, migration and invasive ability. Concordantly, knockdown of ZNF307 increased cell proliferation, migration and invasive ability of HCC cell lines MHCC97L and QGY7701. In vivo functional studies showed that upregulation of ZNF307 expression in Bel7402 cells led to a suppression of tumorigenicity in mice, while knockdown of ZNF307 in MHCC97L cells resulted in reverse. effects. Importantly, flow cytometric analysis showed that ZNF307 overexpression increased the incidence of apoptosis, while ZNF307 knockdown decreased the incidence of apoptosis. Consistently, key regulators in apoptosis, such as caspase-3, BAX and BCL-2 were also regulated by ZNF307. Therefore, our results indicate that ZNF307 may serve as a tumor suppressor and inhibits cell proliferation of HCC via inducing apoptosis.

Objective To explore the clinical effect of radiofrequency ablation(RFA)combined with percutaneous vertebral plasty( PVP)in the treatment of spinal metastatic tumors. Methods After multi-point RFA treatment was provided for the 28 patients with spinal metastatic tumors,self-setting calcium phosphate cement( CPC )was injected for PVP;and then the postoperative complications and postoperative vertebral stability and recurrence were observed. By use of visual analogue score( VAS)and spinal ODI score,pain and spinal function of the patients before the operation and within one month,three months,six months,nine months,and twelve months after the operation were compared and analyzed. Resuits All patients were operated successfully,without serious complications. During the follow-up period of twelve months,there were no spinal metastasis recurrence and no frature in all cases. Within twelve months after the operation,Cobb angles had no significant change from the preoperative ones. Within one month after the operation,the VAS and ODI scores decreased significantly(p <0. 01)and maintained a stable level,and there were no significant difference between the cases within twelve months and one month after the operation(p>0. 05). Conciusion RFA combined with artificial bone PVP in treatment of spinal metastatic tumors has obvious effect,and can maintain long-term vertebral stability.

Objective To explore the effects of radiofrequency ablation ( RFA) combined with percutaneous vertebroplasty ( PVP) by the injection of artificial bone for metastatic spinal tumor. Methods Fifty-eight patients with metastatic spinal tumors were divided into bone cement group 1 (n=12),bone cement group 2 (n=16), artificial bone group 1 (n=16), artificial bone group 2 (n=14). The patients in bone cement group were arranged RFA combined with PVP by injection of bone cement,and the artificial bone group were treated with RFA combined with PVP by injection of artificial bone. The vertebral body modality,fractures, and visual analogue scale ( VAS) ,spinal ODI score were compared before operation,1 week,1,3,6,9,12 months of after operation. Results There were 12 patients (42. 9%) with vertebral body deformation in bone cement group,which was more than those in artificial group (6. 7%) (χ2 =8. 4768,P=0. 0036). The VAS or DOI score decreased after operation than those pre-operation in the 4 groups (P<0. 01),but increased in bone cement group after operation of 6, 9 and 12 months than those in artificial group (P<0. 05). Conclusion The combination of RFA and PVP by injection of bone cement or&nbsp;artificial bone is effective to metastatic spinal tumors. The effects of PVP injection with artificial bone maintains longer duration compared to bone cement.

<正>我院从2010年3月至2011年2月,采用微型外固定架治疗开放性粉碎性指骨骨折26例(31处),经过6~11个月随访,均获得满意效果。现报告如下。1资料与方法1.1一般资料26例31处骨折。男19例,女7例;年龄17~56岁,平均35.4岁;中节指骨骨折16处,近节指骨骨折15处;致伤原因:重物砸伤14例,挤压伤10例,电锯伤2例;合并肌腱断裂19处,伴有骨缺损8处。1.2手术方法常规术前准备,臂丛

目的探讨全关节置换术(TKA)术后并发髌股关节不稳定的危险因素,为提高TKA手术疗效提供参考。方法以TKA后发生髌骨关节不稳定者98例为研究组,未出现髌股关节不稳的130例患者作为对照组,对两组患者的一般情况、TKA直接病因、手术情况、术后并发症等多方面危险因素进行单因素方差分析及多因素回归分析。结果研究组体重指数明显高于对照组(P<0.05),TKA的直接病因在研究组与对照组中所占比例均无显著差异。研究组中,髌骨置换、假体植入位置不良、假体型号不符、肢体力线不佳的比例均显著高于对照组,研究组感染及假体周围骨折的发生率较对照组明显增高。多因素回归分析筛选出5个危险因素,包括关节面置换、植入位置不良、假体型号不符、肢体力线不佳及术后并发感染。结论髌骨置换、假体植入位置不良、假体型号不符、肢体力线不佳及术后并发感染这5个因素是TKA术后并发髌股关节不稳定的独立危险因素。

Objective To explore the long-term effect of microtraumtic discectomy (M TA) in the treatment of lumbar disc herniation disease .Methods 86 patients with lubar intervertebral disc protrusion arranged M TD were followed up for 5 years ,The Japanese orthopaedic society assessment of treatment (JOA) score and maintained cura-tive effects were analyzed .Results The symptom score was increased until 6 months(23 .1 ± 5 .8) ,1 year (24 .8 ± 4 .2) ,2 years (24 .9 ± 4 .3) and 5 years (24 .5 ± 4 .6) after operation compared to preoperation (6 .2 ± 1 .8) (P<0 . 01) .Symptom improvement rate of JOA for optimal had 48 cases (85 .7% ) ,benign in 6 cases (10 .7% ) ,and poor in 1 case (1 .8% ) Long-term follow-up indicated that curative effect was stable .Conclusion M TD in patients with lum-bar disc herniation could be with significant long-term efficacy and stableness ,and could be carried out at all levels of hospitals on the basis of accurate positioning and skilled in operating essentials .

Objective To explore the outcome of minimally invasive spine surgical technique for osteoporotic vertebral compression fractures .Methods 110 patients with osteoporotic vertebral compression fractures were ran-domly divided into percutaneous kyphoplasty (PKP) treatment group (PKP group ,55 cases) and open surgery treat-ment group (control group ,55 cases) ,and treated respectively .Clinical therapeutic effectiveness were compared be-tween the two groups three months after treatment .Results Compared with control group ,mean operating time and blood loss were significantly lower (P<0 .05) .Compared with before treatment ,the VAS scores after treatment of ODI and Cobb Angle were significantly decreased ,and the SF-36 was significantly increased (P<0 .05) .But after treatment ,SF-36 and Cobb Angle of PKP group were significantly increased than control group (P<0 .05) ,while ODI and VAS score were with no statistical difference (P>0 .05) .Conclusion PKP might be safe and effective for the therapy of spinal osteoporosis compression fractures with advantages of minimally invasive ,but indication should be considered .