BACKGROUND: Long non-coding RNA colon cancer-associated transcript 1 (CCAT1) is involved in transforming multiple cancers into malignant cancer types. Previous studies underlining the mechanisms of the functions of CCAT1 primarily focused on its decoy for miRNAs (micro RNAs). However, the regulatory mechanism of CCAT1-protein interaction associated with tumor metastasis is still largely unknown. The present study aimed to identify proteome-wide CCAT1 partners and explored the CCAT1-protein interaction mediated tumor metastasis. METHODS: CCAT1-proteins complexes were purified and identified using RNA antisense purification coupled with the mass spectrometry (RAP-MS) method. The database for annotation, visualization, and integrated discovery and database for eukaryotic RNA binding proteins (EuRBPDB) websites were used to bioinformatic analyzing CCAT1 binding proteins. RNA pull-down and RNA immunoprecipitation were used to validate CCAT1-Vimentin interaction. Transwell assay was used to evaluate the migration and invasion abilities of HeLa cells. RESULTS: RAP-MS method worked well by culturing cells with nucleoside analog 4-thiouridine, and cross-linking was performed using 365 nm wavelength ultraviolet. There were 631 proteins identified, out of which about 60% were RNA binding proteins recorded by the EuRBPDB database. Vimentin was one of the CCAT1 binding proteins and participated in the tumor metastasis pathway. Knocked down vimetin ( VIM ) and rescued the downregulation by overexpressing CCAT1 demonstrated that CCAT1 could enhance tumor migration and invasion abilities by stabilizing Vimentin protein. CONCLUSION CCAT1 may bind with and stabilize Vimentin protein, thus enhancing cancer cell migration and invasion abilities.
Humans ; HeLa Cells ; RNA, Long Noncoding/metabolism* ; Cell Line, Tumor ; Cell Proliferation/genetics* ; Vimentin/metabolism* ; MicroRNAs/metabolism* ; Colonic Neoplasms/genetics* ; RNA-Binding Proteins/metabolism* ; Gene Expression Regulation, Neoplastic/genetics* ; Cell Movement/genetics*

Stroma surrounding the tumor cells plays crucial roles for tumor progression. However, little is known about the factors that maintain the symbiosis between stroma and tumor cells. In this study, we found that the transcriptional regulator-signal transducer and activator of transcription 3 (Stat3) was frequently activated in cancer-associated fibroblasts (CAFs), which was a potent facilitator of tumor malignancy, and formed forward feedback loop with platelet-activating factor receptor (PAFR) both in CAFs and tumor cells. Importantly, PAFR/Stat3 axis connected intercellular signaling crosstalk between CAFs and cancer cells and drove mutual transcriptional programming of these two types of cells. Two central Stat3-related cytokine signaling molecules-interleukin 6 (IL-6) and IL-11 played the critical role in the process of PAFR/Stat3 axis-mediated communication between tumor and CAFs. Pharmacological inhibition of PAFR and Stat3 activities effectively reduced tumor progression using CAFs/tumor co-culture xenograft model. Our study reveals that PAFR/Stat3 axis enhances the interaction between tumor and its associated stroma and suggests that targeting this axis can be an effective therapeutic strategy against tumor malignancy.

Objective:To promote the development of basic research, clarify the development trend of frontier biotechnology, and strengthen scientific research management in project management, resource integration, risk supervision and other aspects.Methods:Through literature study and expert discussion, this paper analyzed the hot spots of frontier biotechnology research, and put forward suggestions for optimizing strategic tasks and innovation management from the perspective of innovation management.Results:The research of frontier biotechnology in our country showed a rapid development trend, but also faced with challenges such as insufficient technological innovation ability and relatively lagging management level. It is imperative to explore and establish a new scientific research management model and optimize the operation mechanism.Conclusions:The major research achievements of frontier biotechnology are emerging constantly, showing a trend of multi-disciplinary and multi-field integration. China should actively explore innovative management models, optimize and improve strategic tasks, improve the efficiency of scientific research management, and do a good job in supporting the realization of high-level scientific and technological self-reliance.

Among current novel druggable targets, protein–protein interactions (PPIs) are of considerable and growing interest. Diacylglycerol kinase α (DGKα) interacts with focal adhesion kinase (FAK) band 4.1-ezrin-radixin-moesin (FERM) domain to induce the phosphorylation of FAK Tyr397 site and promotes the malignant progression of esophageal squamous cell carcinoma (ESCC) cells. Chrysin is a multi-functional bioactive flavonoid, and possesses potential anticancer activity, whereas little is known about the anticancer activity and exact molecular mechanisms of chrysin in ESCC treatment. In this study, we found that chrysin significantly disrupted the DGKα/FAK signalosome to inhibit FAK-controlled signaling pathways and the malignant progression of ESCC cells both in vitro and in vivo, whereas produced no toxicity to the normal cells. Molecular validation specifically demonstrated that Asp435 site in the catalytic domain of DGKα contributed to chrysin-mediated inhibition of the assembly of DGKα/FAK complex. This study has illustrated DGKα/FAK complex as a target of chrysin for the first time, and provided a direction for the development of natural products-derived PPIs inhibitors in tumor treatment.

外泌体是一种纳米级别的生物膜结构，由机体的多种细胞分泌，广泛分布于唾液、血浆、乳汁等体液中。外泌体中含 有蛋白质、mRNA、miRNA、lncRNA、细胞因子、转录因子受体等多种生物活性物质。肿瘤细胞或肿瘤旁细胞分泌的外泌体可将 一些肿瘤特有的生物信息转移到邻近细胞，甚至远处细胞，并且通过这种细胞间通信传递肿瘤的特性，从而促进肿瘤的发生发 展。本综述旨在着重讨论肿瘤细胞及癌旁细胞分泌的含lncRNA的外泌体对肿瘤微环境，肿瘤的生物学特性的影响，为肿瘤的基 础研究及临床诊断治疗提出新的思路。

肺癌的发病机制非常复杂，目前仍未明确。研究发现miRNA是肿瘤中的一组重要的调节因子，与肺癌的发生发展密 切相关，异常表达后可作为致癌miRNA或抑癌miRNA参与调控信号通路基因的表达，影响肺癌细胞的增殖、迁移、侵袭、转移等 过程。本文就miRNA作为抑癌或致癌基因在肺癌发生发展中机制的最新研究进展进行综述。

[Abstract] MicroRNA (miRNA) is non-coding RNA molecule consisting of 20-25 nucleotides. It plays an important role in regulation of tumorigenesis and progression, including proliferation, differentiation and apoptosis of cancer cells, which directly affect the progress of tumors. Peripheral blood miRNA is relatively more stable, and easier to acquired and detected than tissue miRNA. It is a new generation biomarker for early detection and early diagnosis of tumors. It is also one of the main development directions of research and application in precision medicine. Methods commonly used in peripheral blood miRNA detection are RT-PCR, electrochemical detection, NanoString Technologies, genechip and high-throughput sequencing etc. Multiple miRNAs in peripheral blood are the early diagnostic markers for non-small cell lung cancer, esophageal squamous cell carcinoma, pancreatic cancer, squamous cell carcinoma of the head and neck, ovarian cancer, colorectal cancer, breast cancer, prostate cancer and hematological malignancies. Combined detection of multiple peripheral blood miRNAs, as well as combined detection of tumor-specific miRNAand serological, imaging and other auxiliary methods, can improve the sensitivity and specificity of tumor diagnosis at early stage.

长链非编码RNA（long non-coding RNA，lncRNA）最初被认为是不具有功能的“转录噪声”，但越来越多的研究发现， lncRNA的失调在很多肿瘤中起着癌基因或抑癌基因的作用，是癌症发展的关键分子。PANDAR作为一种重要的lncRNA受到了 诸多关注。有研究证明，PANDAR在许多肿瘤中特异性表达，在大多数肿瘤中上调，但在非小细胞肺癌中显著下调，PANDAR的 特异性表达与肿瘤大小、TNM分期和总生存率显著相关。本文通过对lncRNAPANDAR在恶性肿瘤细胞中的主要作用模式、 表 达情况、作用机制及对各类肿瘤发生发展的影响进行综述，旨在为临床恶性肿瘤生物学诊治疗提供新的靶标。

Objective To investigate the biological effects of exosomes secreted by KYSE410 cells on migration and invasion of KYSE410,KYSE510,YES2 cells and the possible mechanisms underlying the phenotype change.Methods The exosomes were isolated from the conditional supernatant of esophageal cancer cell line KYSE410 by ultracentrifugation.The morphology of exosomes was observed by transmission electron microscopy (TEM).Western blotting was used to detect the protein markers of exosomes.The uptaken of fluorescence-labeled KYSE410 exosomes by KYSE410,KYSE510 and YES2 was also recorded under confocal microscopy.Migration and invasion ability of the three esophageal carcinoma cell lines and the effects of exosomes from KYSE410 on migration and invasion of KYSE410,KYSE510 and YES2 cells were analyzed by Transwell chamber,respectively.The alteration of Wnt/β-catenin and PI3K/Akt pathway-related proteins were detected by Western blotting.Results The membrane structure of KYSE410 derived exosomes could be observed with its diameter ranged between 30-100nm.The invasion and migration ability of three esophageal cancer cells are KYSE410＞ KYSE510＞ YES2.KYSE410 exosomes promoted the migration and invasion of KYSE410,KYSE510 and YES2 cells.Conclusions Concentrated exosomes derived from the highly migratory and invasive esophageal cancer cell line KYSE410 promoted the migration and invasion potentials of itself and esophageal cancer cell lines KYSE510 and YES2,which possibly exerted the effects by activating Wnt/β-catenin and PI3K/Akt signaling pathways.

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers in China, but the underlying molecular mechanism of ESCC is still unclear. Involvement of micro-RNAs has been demonstrated in cancer initiation and progression. Despite the reported function of miR-503 in several human cancers, its detailed anti-oncogenic role and clinical significance in ESCC remain undefined. In this study, we examined miR-503 expression by qPCR and found the downregulation of miR-503 expression in ESCC tissue relative to adjacent normal tissues. Fur-ther investigation in the effect of miR-503 on ESCC cell proliferation, migration, and invasion showed that enhanced expression of miR-503 inhibited ESCC aggressive phenotype and overexpres-sion of CCND1 reversed the effect of miR-503-mediated ESCC cell aggressive phenotype. Our study further identified CCND1 as the target gene of miR-503. Thus, miR-503 functions as a tumor suppressor and has an important role in ESCC by targeting CCND1.