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The supplement of non-covalent interaction can be used to explain the current difference of molecules with similar excluded volume in nanopore experiments.

Background: Overexpression of LSD1 is associated with the occurrence of many diseases, including cancers, which makes LSD1 a significant target for anticancer drug research. Methodology & Results: With the aid of 3D quantitative structure–activity relationship models established with 34 reported resveratrol derivative LSD1 inhibitors, derivatives 35–40 were designed. Absorption, distribution, metabolism and excretion calculations showed that they may have good bioavailability and drug likeness. Additionally, 35 and 37 presented good antitumor effects in an in vitro antiproliferative assay. Molecular docking and molecular dynamics simulation results indicated that 35 and 37 can establish extensive interactions with LSD1. Conclusion: The results of computational prediction and experimental validation suggest that 35 and 37 are effective antitumor inhibitors, which provides some ideas and directions for the development of new anticancer LSD1 inhibitors.

Recent studies have shown that the activation of PI3K/AKT signaling pathway is an essential molecular mechanism participating in trastuzumab resistance in HER2 + GC (gastric cancer). However, how can we effectively inhibit AKT activity associated with drug resistance during trastuzumab treatment? Screening inhibitors against the upstream receptors of PI3K/AKT signaling pathway or interacting proteins of members has become an important way.In this study, western blot, qRT-PCR, CCK8, Co-IP and other techniques were used to explore possible mechanisms participating in trastuzumab resistance in vitro. Besides, the xenograft mouse model and GC tissue samples from patients were used to further validate the in-vitro results.The expression of XB130 adaptor protein was remarkably increased in GC cell lines resistant to trastuzumab, and knockdown of XB130 could reverse the resistance via downregulating p-AKT. In addition, p-SRC (Tyr416) was increased in resistant cells, which could facilitate the binding of XB130 to PI3K p85α. It was also discovered that XB130 could negatively regulate PTEN gene transcription, and thus a positive feedback loop was formed between SRC-XB130-PTEN.In HER2 + GC, XB130 contributes to trastuzumab resistance by stimulating the PI3K/AKT signaling pathway through binding to PI3K p85α under the mediation of SRC kinase and regulating PTEN gene transcription, and in turn forming a positive feedback loop between SRC-XB130-PTEN.

MicroRNAs (miRNAs) play an essential role in the self-renewal of breast cancer stem cells (BCCs). Our study aimed to clarify the role of proto-oncogene c-Jun-regulated miR-5188 in breast cancer progression and its association with Timeless-mediated cancer stemness. In the present study, we showed that miR-5188 exerted an oncogenic effect by inducing breast cancer stemness, proliferation, metastasis, and chemoresistance in vitro and in vivo. The mechanistic analysis demonstrated that miR-5188 directly targeted FOXO1, which interacted with β-catenin in the cytoplasm, facilitated β-catenin degradation, and impaired the nuclear accumulation of β-catenin, thus stimulating the activation of known Wnt targets, epithelial-mesenchymal transition (EMT) markers, and key regulators of cancer stemness. Moreover, miR-5188 potentiated Wnt/β-catenin/c-Jun signaling to promote breast cancer progression. Interestingly, c-Jun enhanced miR-5188 transcription to form a positive regulatory loop, and Timeless interacted with Sp1/c-Jun to induce miR-5188 expression by promoting c-Jun-mediated transcription, which further activated miR-5188-FOXO1/β-catenin-c-Jun loop and facilitated breast cancer progression. Importantly, miR-5188 was upregulated in breast cancer and was positively correlated with poor patient prognosis. This study identifies miR-5188 as a novel oncomiR and provides a new theoretical basis for the clinical use of miR-5188 antagonists in the treatment of breast cancer.

Drought is a major abiotic factor that adversely affects plant growth and crop productivity. Abscisic acid (ABA) and melatonin (MT) are two commonly used hormones, whose exogenous application has been shown to improve crop drought tolerance under water deficiency, when used separately; however, studies on the effects of their combined application on crops are scarce. To amend this, pot studies were conducted to study the effects of exogenous ABA and MT application (single or combined) on cotton leaf photosynthetic carbon metabolism and yield under drought. Results revealed that single ABA or MT application significantly improved plant water status under drought by different pathways, which curtailed drought-induced yield losses. ABA+MT application effects on plant water status were similar to those of MT, however, ABA+MT application had synergistic effects on alleviating drought-induced yield losses. ABA spraying had no effects on the net photosynthetic rate (Pn) of drought-stressed leaves, but MT application improved Pn by increasing stomatal conductance and CO2 fixation, and ABA+MT was more effective than MT in alleviating the Pn. Furthermore, ABA application reduced leaf sucrose synthesis by decreasing sucrose synthase (SuSy) activity, and MT and ABA+MT application also inhibited sucrose synthesis by reducing SuSy and sucrose phosphate synthase activities. Extra ABA down-regulated acid invertase activity to inhibit the hydrolysis of sucrose to hexose, but MT spraying decreased both acid and alkaline invertases activities of drought-stressed leaves, and ABA+MT had similar effects as MT. Although ABA or MT down-regulated GhSWEET5, GhSWEET20 and GhSWEET55 expression, thus repressing sucrose transport to the cell wall, their application up-regulated GhSUT3A/D and GhSUT4 expression in drought-stressed leaves, improving in that way sucrose transport to the sieve-companion cell complex and ultimately benefiting yield formation. Similarly, ABA+MT application had additive effects on GhSUT3A/D and GhSUT4 expression under drought. Consequently, ABA or MT application decreased sucrose content in drought-stressed leaves, while ABA+MT application showed a synergistic effect. Hexose, as the substrate for starch biosynthesis, content decreased in ABA- or MT-treated leaves under drought, however, starch accumulation was not affected by ABA application, and MT spraying increased starch content of drought-stressed leaves, by increasing ADP-glucose pyrophosphorylase activity. Nevertheless, ABA+MT application was more effective in increasing starch synthesis under drought than either single hormone application. In conclusion, the effects of ABA+MT on photosynthetic carbon metabolism of cotton leaves were more similar to those of MT under drought, but there were significant synergistic effects in mitigating the negative effects of drought on Pn, sucrose accumulation, sucrose transport, starch synthesis as well as final yield.

Studies on next point-of-interest (POI) recommendation mainly seek to learn users' transition patterns with certain historical check-ins. However, in reality, users' movements are typically uncertain (i.e., fuzzy and incomplete) where most existing methods suffer from the transition pattern vanishing issue. To ease this issue, we propose a novel interactive multi-task learning (iMTL) framework to better exploit the interplay between activity and location preference. Specifically, iMTL introduces: (1) temporal-aware activity encoder equipped with fuzzy characterization over uncertain check-ins to unveil the latent activity transition patterns; (2) spatial-aware location preference encoder to capture the latent location transition patterns; and (3) task-specific decoder to make use of the learned latent transition patterns and enhance both activity and location prediction tasks in an interactive manner. Extensive experiments on three real-world datasets show the superiority of iMTL.

OBJECTIVE: To compare the histopathological features of the synovium between rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: We retrospectively analyzed the synovial specimens obtained after synovial surgery in 72 cases of RA and 24 cases of OA. Two independent pathologists reviewed the sections of the synovial tissues with HE staining, quantitatively scored the degree of fibroblast-like synoviocyte (FLS) hyperplasia, vascular hyperplasia, fibroplasia, and lymphocyte infiltration, and examined the presence plasma cell infiltration. The pathological morphology of the synovial tissues was evaluated in relation with the clinical data of the patients. RESULTS: Pannus formation was also detected in the synovium of OA patients, which showed a lesser degree of OA-FLS hyperplasia, fibrosis and lymphocyte infiltration and a significantly lower rate of plasma cell infiltration compared with the pannus in RA patients. Vascular proliferation was also milder in the pannus of OA patients than in RA pannus, but the difference was not statistically significant. In OA patients, the pannus could be observed under a microscope and was difficult to distinguish from that in RA patients. CONCLUSION: Pannus formation occurs also in the synovium of OA patients but with milder FLS hyperplasia, fibrosis and lymphocyte infiltration and a lower rate of plasma cell infiltration compared with the pannus in RA patients. These differences in the pannus between OA and RA can be of potential value in the diagnosis and treatment of the patients.

MicroRNA-21 (miR-21) has been revealed to play a crucial role in regulating the biological behavior, including proliferation, migration, invasion and metastasis in certain cancers. However, its role in esophageal squamous cell carcinoma (ESCC) has yet to be elucidated. Based on the data of {"type":"entrez-geo","attrs":{"text":"GSE13937","term_id":"13937"}}GSE13937 downloaded from Gene Expression Omnibus (GEO) database, miR-21 was revealed to be one of the top 20 differentially expressed (DE) miRNAs screened using the Morpheus online tool. RAS p21 protein activator 1 (RASA1) was predicted as the target gene of miR-21 using the predicting software and was combined with miR-21 using the luciferase reporter assay. Its relative expression was significantly decreased, however, miR-21 was increased in the tumor tissues compared to the normal adjacent tissues in patients with ESCC as determined by quantitative polymerase chain reaction (q-PCR). Furthermore, overexpression of miR-21 (mimic) could significantly decrease the gene level of RASA1. Conversely, downregulation of miR-21 (inhibitor) significantly increased the gene level of RASA1, while downregulation of RASA1 (siRASA1) markedly increased the gene expression of miR-21. Notably, the expression of Snail and vimentin were significantly increased by upregulation of miR-21 and downregulation of RASA1. Transwell results revealed that miR-21 and RASA1 regulated proliferation, migration and invasion in ESCC cells. In an in vivo model, miR-21 inhibitor (antagomir) could inhibit tumor growth. In conclusion, miR-21 regulated cell proliferation, migration, invasion and tumor growth of ESCC by directly targeting RASA1, which may have been achieved via regulation of Snail and vimentin. Anti-miR-21 revealed an antitumor effect. Thus, it may be considered as a possible target for ESCC therapy.

In this paper, two types of the foam-filled tubes (FFTs), including O-FFTs and T6-FFTs, were prepared by directly inserting Al foams (AFs) into 6061-O Al alloy empty tubes (O-ETs) and 6061-T6 Al alloy empty tubes (T6-ETs), respectively. Quasi-static compression tests of studied specimens were carried out using an environmental chamber under the temperatures ranging from 25 °C to 250 °C. The results show that the mechanical properties of FFTs decrease with temperature increasing. The T6-FFTs show better energy absorption capacities while the deformation modes are less stable than the O-FFTs. The T6-ETs and T6-FFTs change the deformation mode when the temperature is higher than 150 °C. Both of the number of defects and the lengths of cracks decrease for the T6-FFTs with the increment of temperature. A couple of criteria are proposed to effectively describe and predict the deformation mode of FFTs under quasi-static compression.

Plastic debris represents one of the most prevalent and persistent pollution problems in the marine environment. In particular, microplastics that are mainly degraded from larger plastic debris have become a growing environmental concern. However, studies on the degradation of plastics in the aquatic environment that hydrobios reside in have been limited, while several studies regarding the degradation of plastics have been conducted under outdoor or accelerated weathering conditions. Thus, observation of the degradation of three types of virgin plastic pellets exposed to UV irradiation in three different environments (i.e., simulated seawater, ultrapure water, and a waterless (air) condition) was carried out. Data on the changes in physical and chemical properties were collected. The FTIR spectra showed that hydroxyl groups and carbonyl groups developed in three types of weathered plastic pellets under the air and ultrapure water environmental conditions after 3months of UV irradiation, while only carbonyl groups were found in plastic pellets in the simulated seawater environment. In contrast, the Raman spectra showed no significant changes in the weathered plastic pellets, but there were different intensities of characteristic peaks after exposure to UV irradiation. In addition, SEM images illustrated that granular oxidation, cracks and flakes were common patterns during degradation, and the plastic pellets in the three different environments experienced different levels of chemical weathering. We suggest that further studies on the degradation processes of plastic debris are needed to predict the fate of plastic debris in the environment.

Background Breast cancer is the most common malignancy and the leading cause of cancer death among women. TIMELESS (TIM), a circadian rhythm regulator, has been recently implicated in the progression of human cancer. However, the role of TIM in the progression of breast cancer has not been well-characterized. Methods Immunohistochemistry (IHC) staining was used to examine TIM levels in breast cancer specimens. Mammosphere formation analysis and side population analysis were used to examine the effect of TIM on the self-renewal of breast cancer stem cells. A wound healing assay and a Transwell assay were used to determine the role of TIM in breast cancer cell migration and invasion. A soft agar growth assay in vitro and tumorigenicity in vivo were used to determine the role of TIM in tumorigenicity. Results TIM levels in both breast cancer cell lines and tissues were significantly upregulated. Patients with high TIM had poorer prognosis than patients with low TIM. Overexpression of TIM dramatically enhanced, while knockdown of TIM suppressed the self-renewal of cancer stem cells (CSCs), cell invasion and migration abilities of breast cancer cells in vitro. Moreover, overexpression of TIM significantly augmented, while knockdown of TIM reduced the tumorigenicity of breast cancer cells in vivo. Mechanism studies revealed that TIM upregulated the expression and the trans-activity of the well-known oncogene MYC. Inhibition of MYC significantly blocked the effects of TIM on CSC population, cell invasion and anchor-independent cell growth. Conclusion TIM plays an important role in promoting breast cancer progression and may represent a novel therapeutic target for breast cancer. Electronic supplementary material The online version of this article (doi:10.1186/s13058-017-0838-1) contains supplementary material, which is available to authorized users.

The clinicopathological characteristics of breast cancer patient samples (DOCX 14 kb)

The present study examined a correlation between CXC chemokine ligand 16 (CXCL16) and cell differentiation antigen 99 (CD99) expression and investigated the role of CXCL16 in human lymphoma cell lines and clinical samples. Cytokine antibody arrays were used to measure the differentially expressed cytokines in tumor tissues. The expression of CXCL16 and CD99 was analyzed by quantitative PCR (qPCR) and western blotting, while the pathways involved were assessed by western blotting and enzyme-linked immunosorbent assay (ELISA). The expression of CXCL16 was investigated in 9 lymphoma cell lines (L428, RPMI-8226, KM3, Jurkat, OCI-Ly1, OCI-Ly8, OCI-Ly10, Karpass299 and Raji) as well as in clinical lymphoma samples using qPCR, western blotting and immunochemistry. Soluble CXCL16 (sCXCL16) levels were measured by ELISA and proliferation was analyzed by CCK‑8 proliferation assays. CXCL16 was one of the upregulated chemokines when lymphoma cells where transferred from in vitro to in vivo conditions. The increased expression and secretion of CXCL16 paralleled with a decrease of mCD99L2 and was accompanied by NF-κB pathway activation and vice versa. CXCL16 was expressed in all 9 lymphoma cell lines with the highest levels in the Hodgkin lymphoma (HL) cell line L428, the plasma cell-derived cell lines RPMI‑8226 and KM3 and the T leukemia-derived cell line Jurkat. Higher levels of sCXCL16 were secreted by L428 cells, the diffuse large B-cell lymphoma (DLBCL)-derived cell lines (OCI-Ly1, OCI-Ly8 and OCI-Ly10) and Jurkat cells. CXCL16 was widely expressed in clinical samples of lymphoma patients with higher levels in HL compared to non-Hodgkin lymphoma. Human recombinant CXCL16 had no significant effect on L428 cell proliferation, but was able to stimulate CD4+ T lymphocytes to proliferate. CXCL16, inversely correlated with CD99 expression in Hodgkin Reed-Sternberg (H/RS) cells, is widely expressed in diverse types of lymphomas.

BACKGROUND Accumulating evidence indicates that microRNAs play a pivotal role in the development and progression of prostate cancer. The present study was aimed at clarifying the biological functions of miR-153, one of the upregulated microRNAs in prostate cancers, and the signaling transduction induced by miR-153. METHODS miR-153 was identified to be overexpressed in prostate cancers. The probable biological function of miR-153 in cellular proliferation was then examined by diverse assays, such as MTT, colony formation and BrdUrd incorporation assay. Moreover, real-time PCR and western blotting analysis were applied to investigate the underlying molecular mechanism induced by miR-153. Luciferase assays were used to determined the FOXO1 transactivity and the direct regulation of PTEN-3′-UTR by miR-153. RESULTS High-throughput method identified miR-153 to be upregulated in prostate cancers, which is further confirmed by the upregulated expression in four paired prostate tumor/adjacent non-cancerous tissues from the same patients. Further studies revealed that overexpression of miR-153 promoted cell cycle transition and cell proliferation, while inhibition of miR-153 reduced this effect. Moreover, miR-153 overexpression in prostate cancer cells increased the G1/S transitional promoter, cyclin D1 expression, and decreased cyclin-dependent kinase (CDK) inhibitor, p21Cip1expression. In addition, we demonstrated that miR-153 directly targeted the PTEN tumor suppressor gene, activated the AKT signaling and downregulated FOXO1 transcriptional activity. CONCLUSIONS Taken together, our results suggest that miR-153 play an important role in promoting proliferation of human prostate cancer cells and present a novel mechanism of microRNA-mediated direct suppression of PTEN expression in prostate cancer cells. Prostate 73: 596–604, 2013. © 2012 Wiley Periodicals, Inc.

Hodgkin’s lymphoma (HL) is a lymphoid neoplasm characterized by Hodgkin’s and Reed-Sternberg (H/RS) cells, which is regulated by CD99. We previously reported that CD99 downregulation led to the transformation of murine B lymphoma cells (A20) into cells with an H/RS phenotype, while CD99 upregulation induced differentiation of classical Hodgkin’s lymphoma (cHL) cells (L428) into terminal B-cells. However, the molecular mechanism remains unclear. In this study, using fluorescence two-dimensional differential in-gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS), we have analyzed the alteration of protein expression following CD99 upregulation in L428 cells as well as downregulation of mouse CD99 antigen-like 2 (mCD99L2) in A20 cells. Bioinformatics analysis showed that SEPTIN2 and STATHMIN, which are cytoskeleton proteins, were significantly differentially expressed, and chosen for further validation and functional analysis. Differential expression of SEPTIN2 was found in both models and was inversely correlated with CD99 expression. STATHMIN was identified in the A20 cell line model and its expression was positively correlated with that of CD99. Importantly, silencing of SEPTIN2 with siRNA substantially altered the cellular cytoskeleton in L428 cells. The downregulation of STATHMIN by siRNA promoted the differentiation of H/RS cells toward terminal B-cells. These results suggest that SEPTIN2-mediated cytoskeletal rearrangement and STATHMIN-mediated differentiation may contribute to changes in cell morphology and differentiation of H/RS cells with CD99 upregulation in HL.

To determine the optimal dosing of streptozotocin (STZ) for establishing lymphoma-bearing diabetic mouse models.A total of 200 healthy male Balb/c mice were randomized into 4 groups (n=50) for intraperitoneal injection of a single dose of vehicle solution (control) or 75, 150, or 200 mg/kg STZ. The changes of body weight and blood glucose were observed regularly, and the success rate of modeling, mortality rate, and survival of the mice were recorded after the injections. The mice with successfully induced diabetes received subcutaneous or tail vein injection of A20 lymphoma cells, and the rate of tumorigenesis, mortality rate, and survival time were observed at 1 month and 3 months after tumor cell injection.Compared with the control group, the mice receiving STZ injection at 150 and 200 mg/kg showed significantly decreased body weight and increased blood glucose (P0.05), while STZ at 75 mg/kg did not produced such obvious changes. STZ injection at 200 mg/kg resulted in a significantly higher mortality rate and shorter survival time than STZ at 150 mg/kg (P0.05). In the control group and 150 and 200 mg/kg STZ groups, the rate of tumorigenesis or mortality rate showed no significant differences after subcutaneous injection of A20 lymphoma cells (P0.05), but differed significantly at 3 months after tail vein injection of the tumor cells (P0.05).Intraperitoneal injection of STZ at 150 mg/kg is associated with a low mortality rate, a high successful modeling rate of diabetes and a long survival time in mice, and is therefore optimal for establishing diabetic mouse models bearing transplanted tumors.

We report a case of multiple endocrine neoplasia (MEN) type 2A and summarize the clinical characteristics, diagnosis and treatment of this condition. The diagnosis of MEN type 2A relies on a comprehensive evaluation of the findings of ultrasound, CT and laboratory examinations, and early diagnosis and treatment is critical to improving the prognosis. Genetic testing of RET is the gold standard for diagnosis of MEN type 2A and 2B. Surgical intervention currently remains the primary choice of treatments of this disease.

There is much evidence suggesting that CCL5 is one of the chemoattractant cytokines involved in diabetes mellitus (DM) with diffuse large B‑cell lymphoma (DLBCL). However, the pathological impact is unclear. In the current study, in order to improve understanding regarding the role of CCL5 in DM with DLBCL, the expression levels of CCL5 mRNA were examined in normal B cells, human DLBCL cell lines (Ly1, Ly8 and Ly10) and a mouse DLBCL cell line (A20), as well as those in cells cultured with either 5 or 30 mmol/l glucose. A20‑CCL5+ (CCL5 overexpression) and A20‑CCL5‑ (CCL5 knockdown) subclones were obtained through cell transduction with a lentiviral vector, and were subcutaneously injected into BALB/c DM mice and normal mice. Tumor growth was observed by calculating the tumor volume. The results demonstrated that CCL5 mRNA levels in DLBCL cells were significantly higher than those in the normal cells (P

Mouse CD99 antigen-like 2 (mCD99L2) has previously been confirmed to be expressed in murine B lymphoma (A20) cells by our group. The present study aimed to establish a mCD99L2‑downregulated A20 cell line and to investigate the effect of shRNA targeting mCD99L2 in A20 cells in vitro and in vivo. Four pLenti6/mCD99L2 expression vectors containing the mCD99L2 shRNA-expressing cassette were constructed, transfected into A20 cells and stable mCD99L2-downregulated A20 subclones, termed A20-mCD99L2- cells, were established and identified by quantitative PCR and western blot analysis. Light and transmission electron microscopy, MTT assay, flow cytometry and immunofluorenscence labeling were used to observe the morphological, biological and phenotypic characteristics in vitro. Some of the A20-mCD99L2- cells exhibited H/RS‑cell like morphology, a decreased proliferative ability, a prolonged G2 phase and increased CD30 and CD15 expression. Upon injecting cells into nude or immunocompetent BALB/c mice, tumorigenesis, tumor growth, morphology and phenotypes in vivo were observed. A20-mCD99L2- cells induced tumors in nude and BALB/c mice, but with less potency in the latter compared with the controls. Similar morphological, biological and phenotypic characteristics were observed in the A20-mCD99L2- cell-induced tumors as those in vitro. Several cytokines including CD30T, IL-12p40/p70, IL-3, IFN-γ, CXCL16, MIP-1α and CD40 were upregulated following mCD99L2 downregulation when detected using antibody arrays. The results from western blot analysis indicated that the regulation of mCD99L2 expression may involve the activated nuclear factor-κB pathway in the murine B lymphoma cells. The present study provides data for further investigation into the mCD99L2 gene in tumor cells.

Forkhead box protein O1 (FOXO1), a key member of the FOXO family of transcription factors, acts as a tumor suppressor and has been associated with various key cellular functions, including cell growth, differentiation, apoptosis and angiogenesis. Therefore, it is puzzling why FOXO protein expression is downregulated in cancer cells. MicroRNAs, non-coding 20~22 nucleotide single-stranded RNAs, result in translational repression or degradation and gene silencing of their target genes, and significantly contribute to the regulation of gene expression. In the current study, we report that miR-370 expression was significantly upregulated in five prostate cancer cell lines, compared to normal prostatic epithelial (PrEC) cells. Ectopic expression of miR-370 induced proliferation and increased the anchorage-independent growth and colony formation ability of DU145 and LNCaP prostate cancer cells, while inhibition of miR-370 reduced proliferation, anchorage-independent growth and colony formation ability. Furthermore, upregulation of miR-370 promoted the entry of DU145 and LNCaP prostate cancer cells into the G1/S cell cycle transition, which was associated with downregulation of the cyclin-dependent kinase (CDK) inhibitors, p27(Kip1) and p21(Cip1), and upregulation of the cell-cycle regulator cyclin D1 mRNA. Additionally, we demonstrated that miR-370 can downregulate expression of FOXO1 by directly targeting the FOXO1 3'-untranslated region. Taken together, our results suggest that miR-370 plays an important role in the proliferation of human prostate cancer cells, by directly suppressing the tumor suppressor FOXO1.

CCL5 is one of the chemoattractant cytokines involved in inflammatory observed in both diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin's lymphoma (CHL). However, the pathological effects of CCL5 remain unclear. To gain a better understanding of the role of CCL5 in CHL and DLBCL, we examined the expression of CCL5 in the CHL cell line L428 and the DLBCL cell lines Ly1 and Ly8, as well as its chemotactic effect on CD4+ T cells. CCL5 mRNA expression was detected by real-time quantitative RT-PCR. Intracellular CCL5 protein expression was analyzed using confocal microscopy, and CCL5 protein secretion was detected by ELISA. The chemotactic function of CCL5 was assessed using a Transwell coculture system, and the number of migrated CD4+ T cells was counted. Moreover, the p-iкBα and p65 levels of NF-кB signaling molecules in these lymphoma cell lines were detected by Western blotting. The results showed that CCL5 mRNA and protein expression in the L428 cells was significantly higher than in Ly1 and Ly8 cells (p

CD99 is a 32-kDa transmembrane glycoprotein that is encoded by the MIC2 gene. Our study was carried out to examine the role of CD99 in tumor progression of classical Hodgkin lymphoma (cHL). Here, we showed that lowly expressed CD99 protein in cHL cell lines and primary cHL cases correlates with the deficient expression of the positive regulatory domain 1 (PRDM1/BLIMP1). In addition, cHL cell lines showed high levels of miR-9 expression. We determined that the upregulation of CD99 induced expression of transcription factor PRDM1, a master regulator of plasma-cell differentiation, which is also a target for miR-9-mediated downregulation. Indeed, inhibition of miR-9 also triggered upregulation of PRDM1 expression. Furthermore, overexpression of CD99 resulted in changed growth features and reorganization of actin cytoskeleton. As upregulation of CD99 led to a decrease in cHL diagnosis marker CD30 and CD15 and an increase in plasma-cell differentiation marker CD38 and the restoration of B-cell makers PAX5, CD79α and CD19, we suggest that downregulated CD99 leads to the prevention of plasma-cell differentiation in Hodgkin/Reed-Sternberg (H/RS) cells. Furthermore, these data indicate that CD99 may control miR-9 expression, which directly targets PRDM1. Altogether, these results reveal a CD99-miR-9-PRDM1 molecule axis in lymphomagenesis of cHL and suggest that upregulation of CD99 in H/RS cells induces terminal B-cell differentiation, which may provide a novel therapeutic strategies for cHL.