Long noncoding RNA LINC01234 promoted cell proliferation and invasion via miR-1284/TRAF6 axis in colorectal cancer

Colorectal cancer is one of the most common and leading malignancies globally. Long noncoding RNAs (lncRNAs) function as potentially critical regulator in colorectal cancer. LINC01234, a novel lncRNA in tumor biology, regulates the progression of various tumors. However, the tumorigenic mechanism of LINC01234 in colorectal cancer is still unclear. This study was performed with the aim to prospectively investigate clinical significance, effect, and mechanism of lncRNA LINC01234 in colorectal cancer. First, we found that LINC01234, localized in the cytoplasm, was increased in both colorectal cancer cell lines and tissues. Subsequent functional assays suggested LINC01234 knockdown suppressed cell proliferation, migration, and invasion of colorectal cancer cells, while blocked cell cycle and induced cell apoptosis. Moreover, we identified that miR-1284 was target of LINC01234, we further demonstrated a negative correlation with LINC01234 in colorectal cancer tissues and cells. Furthermore, miR-1284 targeted and suppressed tumor necrosis factor receptor–associated factor 6 (TRAF6). Loss-of-function assay revealed that LINC01234 silencing suppressed colorectal cancer progression through inhibition of miR-1284. In vivo subcutaneous xenotransplanted tumor model indicated LINC01234 knockdown inhibited in vivo tumorigenic ability of colorectal cancer via downregulation of TRAF6. Collectively, this study clarified the biological significance of LINC01234/miR-1284/TRAF6 axis in colorectal cancer progression, providing insights into LINC01234 as novel potential therapeutic target for colorectal cancer therapeutic from bench to clinic.     

Protein kinase D1 inhibition interferes with mitosis progression

Protein kinase D1 (PKD1) plays a vital role in signal transduction, cell proliferation, membrane trafficking, and cancer; however, the majority of the studies up to date had centered primarily on PKD1 functions in interphase, very little is known about its role during cell division. We previously demonstrated that during mitosis PKD1 is activated and associated with centrosomes, spindles, and midbodies. However, these observations did not address whether PKD1 was associated with mitosis regulation. Accordingly, we used rapidly acting PKD-specific inhibitors to examine the contribution of PKD1 the sequence of events in mitosis. We found that although PKD1 overexpression did not affect mitosis progression, suppression of its catalytic activity by two structurally unrelated inhibitors (kb NB 142-70 and CRT 0066101) induced a significant delay in metaphase to anaphase transition time. PKD1 inhibition during mitosis also produced the appearance of abnormal spindles, defects in chromosome alignment, and segregation as well as apoptosis. Thus, these observations indicate that PKD1 activity is associated with mitosis regulation.     

Functional roles of PC‐PLC and Cdc20 in the cell cycle,proliferation, and apoptosis

Phosphatidylcholine‐specific phospholipase C (PC‐PLC) is the major enzyme in the Phosphatidylcholine (PC) cycle and is involved in many long‐term cellular responses such as activation, proliferation, and differentiation events. Cell division cycle 20 homolog (Cdc20) is an essential cell‐cycle regulator required for the completion of mitosis. Our previous studies identified the interaction between PC‐PLC and Cdc20. Through the interaction, Cdc20 could mediate the degradation of PC‐PLC by Cdc20‐mediated ubiquitin proteasome pathway (UPP). In this study, we found that PC‐PLC might not be involved in cancer metastasis. Inhibition of PC‐PLC by D609 could cause cell proliferation inhibition and apoptosis inhibition in CBRH‐7919 cells. Inhibition of PC‐PLC could also influence the cell cycle by arresting the cells in G1 phase, and Cdc20 might be involved in these processes. Taken together, in this report, we provided new evidence for the functional roles of PC‐PLC and Cdc20 in the cell cycle, proliferation, and apoptosis in CBRH‐7919 cells. Copyright © 2010 John Wiley & Sons, Ltd.     

传输靶向COX-2 siRNA联合化疗药物对大鼠胃癌细胞生长

目的：通过动物实验探讨传输靶向COX-2 siRNA联合化疗药物对大鼠胃癌细胞生长的抑制作用。方法：24 只健康SD 大鼠 平分为三组,治疗组用COX-2-siRNA转染的胃癌SGC7901 细胞接种,同时进行环磷酰胺、丝裂霉素C 化疗治疗;阴性对照组,用 阴性对照siRNA 转染的胃癌SGC7901 细胞接种,同时进行环磷酰胺、丝裂霉素C 化疗治疗;对照组(n=8),用未经转染的胃癌 SGC7901 细胞接种,不进行化疗治疗;三组转染后都接种了裸鼠。结果：治疗组、阴性对照组及对照组胃癌细胞凋亡率分别为 （22.28± 0.12）%、（1.23± 0.17）%和（1.03± 0.14）%,治疗组与阴性对照组和对照组比较差异都有统计学意义(t=18.152,17.555, P<0.05)。治疗组的抑瘤率为76.7%,阴性对照组和对照组分别为12.8%和6.89%,治疗组的抑瘤率明显高于其他两组(x2=15. 211,13.899,P<0.05)。Western blotting检测结果显示治疗组的COX-2 蛋白表达含量得到了明显抑制。结论：传输靶向COX-2 siRNA和化疗药物的配合应用可有效抑制COX-2 蛋白的表达,从而抑制胃癌细胞的生长,从而起到更好的治疗效果。     

转录因子二聚化配体3（TFDP3）在乳腺癌组织中的表达及其与乳腺癌分子分型的相关性研究

目的:本研究旨在分析总结癌-睾丸抗原TFDP3在乳腺癌中的表达规律,探究TFDP3表达与乳腺癌分型及发病进程关系。方法:通过对不同分型及分期的乳腺癌组织切片进行免疫组化检测,分析TFDP3在其中的表达情况,并结合样本来源患者的临床信息,对TFDP3的表达与乳腺癌分子分型、分期及预后的相关性进行统计分析。同时,通过Western Blot检测了5种乳腺癌细胞系(MDA-MB-231、MCF-7、SK-BR-3、T47D及MCF-10A)中TFDP3的表达情况,并通过细胞免疫荧光实验,检测TFDP3在细胞中的定位。结果:TFDP3在已检测的乳腺癌样本中的表达率为49%。乳腺癌临床分子分型标记物HER2的表达与TFDP3的表达呈正相关,但乳腺癌的分期、临床病理分型以及临床分子分型标记物ER、PR的表达均与肿瘤组织中TFDP3的表达无相关性。结论:TFDP3在各在乳腺癌组织中高表达,其表达量与HER2的表达量呈正性相关。这为研究已TFDP3为靶点的乳腺癌免疫治疗,提供了新的依据。     

Antitumor effect of miR-197 targeting in p53 wild-type lung cancer

Lung cancer is the leading cause of tumor-related death. The lack of effective treatments urges the development of new therapeutic approaches able to selectively kill cancer cells. The connection between aberrant microRNA (miRNA – miR) expression and tumor progression suggests a new strategy to fight cancer by interfering with miRNA function. In this regard, LNAs (locked nucleic acids) have proven to be very promising candidates for miRNA neutralization. Here, we employed an LNA-based anti-miR library in a functional screening to identify putative oncogenic miRNAs in non-small-cell lung cancer (NSCLC). By screening NIH-H460 and A549 cells, miR-197 was identified as a new functional oncomiR, whose downregulation induces p53-dependent lung cancer cell apoptosis and impairs the capacity to establish tumor xenografts in immunodeficient mice. We further identified the two BH3-only proteins NOXA and BMF as new miR-197 targets responsible for induction of apoptosis in p53 wild-type cells, delineating miR-197 as a key survival factor in NSCLC. Thus, we propose the inhibition of miR-197 as a novel therapeutic approach against lung cancer.     

阴道微生态与高危型人乳头瘤病毒感染及宫颈病变的相关性

目的 探究阴道微生态与高危型人乳头瘤病毒(HR HPV)感染以及宫颈病变之间的相关性,为后续研究提供参考。 方法 选择2018年1月至2019年6月就诊于石河子大学医学院第一附属医院妇科门诊,同时行爱必维(细菌性阴道病五项联合测定试剂盒)检测、HR HPV检测及宫颈组织病理检查的343名妇女作为研究对象,分析相关检测数据并探究阴道微生态与HR HPV感染以及宫颈病变的相关性。 结果 过氧化氢阳性、唾液酸苷酶阳性、白细胞酯酶阳性、乳杆菌数量减少及阴道清洁度3~4度的妇女感染HR HPV及发生宫颈病变的可能性显著大于过氧化氢阴性、唾液酸苷酶阴性、白细胞酯酶阴性、乳杆菌数量较多及阴道清洁度1~2度的妇女,差异均有统计学意义(均P结论 阴道微生态失衡与HR HPV感染以及宫颈病变有一定关联,纠正阴道微生态失衡可一定程度上预防HR HPV感染及宫颈病变。     

Epigenetic repression of microRNA-129-2 leads to overexpression of SOX4 in gastric cancer

High levels of SOX4 expression have been found in a variety of human cancers, such as lung, brain and breast cancers. However, the expression of SOX4 in gastric tissues remains unknown. The SOX4 expression was detected using immunohistochemical staining and semi-quantitative RT-PCR, and our results showed that SOX4 was up-regulated in gastric cancer compared to benign gastric tissues. To further elucidate the molecular mechanisms underlying up-regulation of SOX4 in gastric cancers, we analyzed the expression of microRNA-129-2 (miR-129-2) gene, the epigenetic repression of which leads to overexpression of SOX4 in endometrial cancer. We found that up-regulation of SOX4 was inversely associated with the epigenetic silencing of miR-129-2 in gastric cancer, and restoration of miR-129-2 down-regulated SOX4 expression. We also found that inactivation of SOX4 by siRNA and restoration of miR-129-2 induced apoptosis in gastric cancer cells.     

DNMT3b 39179G‎T Polymorphism and the Risk of Adenocarcinoma of the Colon in Koreans

DNA-methyltransferase-3B (DNMT3b) plays an important role in the generation of aberrant methylation in carcinogenesis. DNMT3b SNP has been associated with susceptibility to lung, head, neck, and breast cancer, but its association with the development of colon cancer has not been reported. We investigated the relationship between the 39179G‎T polymorphism in the DNMT3b gene, which is involved in de novo methylation and is associated with the risk of adenocarcinoma of the colon in Koreans. The DNMT3b 39179G‎T genotypes were determined by a PCR-RFLP method in 248 adenocarcinomas of colon cancer patients and in 248 healthy controls matched as to age and sex. When stratified by sex and age, a significantly reduced risk of the combined GT and GG genotypes was observed in younger patients (<59, adjusted OR = 0.255, 95% CI = 0.133–0.489) and in male patients (adjusted OR = 0.383, 95% CI = 0.225–0.652). The DNMT3b 39179G‎T polymorphism may be a genetic determinant of adenocarcinoma of the colon, especially in younger Korean men.