SNHG25 facilitates SNORA50C accumulation to stabilize HDAC1 in neuroblastoma cells.

Increasing studies have pointed out that small nucleolar RNAs (snoRNAs) and their host genes (SNHGs) have multi-functional roles in cancer progression. Bioinformatics analysis revealed the importance of snoRNA host gene 25 (SNHG25) in neuroblastoma (NB). Hence, we further explored the function and molecular mechanism of SNHG25 in NB. Our study revealed that SNHG25 expression was upregulated in NB cells. Through loss-of-function assays, we discovered that silencing of SNHG25 suppressed NB cell proliferation, invasion, and migration. Moreover, we found that SNHG25 positively regulated snoRNA small nucleolar RNA, H/ACA box 50 C (SNORA50C) in NB cells, and SNORA50C depletion had the same function as SNHG25 silencing in NB cells. Moreover, we proved that SNHG25 recruited dyskerin pseudouridine synthase 1 (DKC1) to facilitate SNORA50C accumulation and associated small nucleolar ribonucleoprotein (snoRNP) assembly. In addition, it was manifested that SNHG25 relied on SNORA50C to inhibit ubiquitination of histone deacetylase 1 (HDAC1), thereby elevating HDAC1 expression in NB cells. Further, HDAC1 was proven to be a tumor-facilitator in NB, and SNORA50C contributed to NB cell growth and migration through the HDAC1-mediated pathway. In vivo xenograft experiments further supported that SNHG25 promoted NB progression through SNORA50C/HDAC1 pathway. Our study might provide a novel sight for NB treatment.

TTF1 suppresses neuroblastoma growth and induces neuroblastoma differentiation by targeting TrkA and the miR-204/TrkB axis.

Neuroblastoma (NB) is the most common extracranial malignant solid tumor in children. We found that TTF1, TrkA, and miR-204 were lowly expressed, whereas TrkB was highly expressed in undifferentiated NB tissues. Meanwhile, TTF1 expression correlated positively with TrkA and miR-204 expression but negatively with TrkB expression. The TTF1 promoter was hypermethylated in undifferentiated NB tissues and SK-N-BE cells, leading to TTF1 downregulation. We also identified miR-204, which directly targets TrkB, as a transcriptional target of TTF1. Functionally, TTF1 suppressed proliferation, migration, and invasion of NB cells, whereas induced cell cycle arrest, apoptosis, and autophagy of NB cells by regulating TrkA and the miR-204-TrkB axis. Furthermore, TTF1 suppressed tumor growth and promoted neurogenic differentiation in a NB xenograft mouse model. Our study demonstrates that TTF1 reduces tumor growth and induces neurogenic differentiation in NB by directly targeting TrkA and the miR-204/TrkB axis.

YTHDF2 Gene rs3738067 A>G Polymorphism Decreases Neuroblastoma Risk in Chinese Children: Evidence From an Eight-Center Case-Control Study.

Neuroblastoma is a primary malignancy mainly occurring in children. We have reported that polymorphisms of several N6-methyladenosine (m6A) RNA modification-related genes contributed to neuroblastoma risk in previous studies. YTHDF2, a "reader" of RNA m6A modification, is involved in cancer progression. Here, we estimated the association between a YTHDF2 gene rs3738067 A>G polymorphism and neuroblastoma susceptibility in 898 neuroblastoma patients and 1,734 healthy individuals from China. We found that the rs3738067 A>G could decrease neuroblastoma risk [AG vs. AA: adjusted odds ratio (OR) = 0.76, 95% confidence interval (CI) = 0.64-0.90, P = 0.002; AG/GG vs. AA: adjusted OR = 0.81, 95% CI = 0.69-0.95, P = 0.011). Besides, the rs3738067 AG/GG genotype was related to reduced neuroblastoma risk in the following subgroups: children aged 18 months and under, boys, patients with tumors originating from retroperitoneal, patients at clinical stage IV, and cases at clinical stages III plus IV. Importantly, false-positive report probability analysis proved our significant results worthy of close attention of. The expression quantitative trait locus analysis results revealed that the rs3738067 was associated with the expression of YTHDF2.

Tripartite motif-containing 3 (TRIM3) enhances ER signaling and confers tamoxifen resistance in breast cancer.

Tamoxifen resistance remains a clinical problem in estrogen receptor (ER)-positive breast cancer. SUMOylation of ERα enhances ERα-induced transcription activity. Tripartite motif-containing (TRIM) proteins are a new class of SUMO E3 ligases, which regulate the SUMOylation of proteins. However, the precise molecular mechanism and function of TRIM3 in SUMOylation and the response to tamoxifen remain unclear. In the present study, we observed that TRIM3 was dramatically overexpressed in breast cancer, which correlated with tamoxifen resistance. Furthermore, TRIM3 overexpression significantly correlated with poor survival of patients with ER+ breast cancer treated with tamoxifen. TRIM3 overexpression conferred cell survival and tumorigenesis, whereas knocking down of TRIM3 reduced these capabilities. Moreover, TRIM3, as a ubiquitin carrier protein 9 (UBC9) binding protein, promoted SUMO modification of estrogen receptor 1 (ESR1) and activated the ER pathway. Silencing UBC9 abolished the function of TRIM3 in regulating tamoxifen resistance. These results suggest TRIM3 as a novel biomarker for breast cancer therapy, indicating that inhibiting TRIM3 combined with tamoxifen might provide a potential treatment for breast cancer.

FZD2 promotes TGF-ß-induced epithelial-to-mesenchymal transition in breast cancer via activating notch signaling pathway.

BACKGROUND: Breast cancer (BC) is one of the commonest female cancers, which is characterized with high incidence. Although treatments have been improved, the prognosis of BC patients in advanced stages remains unsatisfactory. Thus, exploration of the molecular mechanisms underneath BC progression is necessary to find novel therapeutic methods. Frizzled class receptor 2 (FZD2) belongs to Frizzled family, which has been proven to promote cell growth and invasion in various human cancers. The purpose of our current study was to detect the functions of FZD2 in BC and explore its underlying molecular mechanism. METHODS: The level of FZD2 was measured in BC tissues by quantitative real-time polymerase chain reaction (qRT-PCR), western blot, immunohistochemistry (IHC), respectively. Cell Counting Kit-8 (CCK-8), colony formation assay, transwell assays, wound healing assay and flow cytometry analyses were separately conducted to detect cell viability, invasion, migration, apoptosis and cell cycle distribution. The levels of Epithelial-mesenchymal transition (EMT) biomarkers were examined by using Immunofluorescence assay. Xenograft tumorigenicity assay was performed to assess the effect of FZD2 on tumor growth in vivo. RESULTS: FZD2 mRNA and protein expression was abundant in BC tissues. Moreover, high level of FZD2 had significant correlation with poor prognosis in BC patients. In vitro functional assays revealed that silencing of FZD2 had suppressive effects on BC cell growth, migration and invasion. Animal study further demonstrated that FZD2 silencing inhibited BC cell growth in vivo. In addition, FZD2 induced EMT process in BC cells in a transforming growth factor (TGF)-ß1-dependent manner. Mechanistically, knockdown of FZD2 led to the inactivation of Notch signaling pathway. CONCLUSION: FZD2 facilitates BC progression and promotes TGF-ß1-inudced EMT process through activating Notch signaling pathway.

Tumor Suppressor Effect of RBMS3 in Breast Cancer.

BACKGROUND: RBMS3 (RNA-binding motif, single-stranded-intervacting protein 3) acts as a tumor-suppressive gene in a number of human cancers, however, its role in breast cancer is not fully understood. This study aimed to investigate the expression and clinicopathological significance of RBMS3 in breast cancer. METHODS: A total of 998 breast cancer tissue samples in The Cancer Genome Atlas (TCGA) database with survival outcomes were divided into high RBMS3 expression and low expression groups using the median as the cutoff. Clinicopathological characteristics and prognosis were compared between the 2 groups. RESULTS: TCGA showed that RBMS3 mRNA was downregulated in breast cancer tissues, and RBMS3 downregulation was correlated with poor prognosis. Immunohistochemistry staining of 127 paraffin-embedded breast cancer tissues showed that RBMS3 protein was localized in the cytoplasm and nucleus; however, nuclear staining was present in 90.0% of normal breast tissues but only 28.3% of breast cancer tissues. Decreased RBMS3 protein expression was significantly correlated with estrogen receptor (ER)-negative status and death at final follow-up. Patients with lower RBMS3 protein expression had substantially shorter survival than those with higher RBMS3 expression. Univariate and multivariate analysis indicated that the combination of RBMS3 expression and ER status (a variable designated as "cofactor") was an independent prognostic factor in patients with breast cancer (hazard ratio [HR] = 0.420, 95% confidence interval [CI]: 0.223-0.791, P = 0.007). CONCLUSION: RBMS3 downregulation was correlated with poor prognosis in breast cancer patients, and the combination of RBMS3 expression and ER status was an independent prognostic factor.

Sensitive quantitation of ESR1 mutations in cell-free DNA from breast cancer patients using base-specific invasive reaction assisted qPCR.

Acquired estrogen receptor 1 (ESR1) mutation is being promoted as a key mechanism of resistance to endocrine therapies in breast cancers. It is significative to monitor ESR1 mutations in real time, which provide an opportunity to alter therapy as these mutations emerge. Previous assays based on next-generation sequencing (NGS) and digital PCR (dPCR) usually due to high costs and complicated workflows hampered their clinical adoption in general medical institutions. Here, we proposed a new strategy using base-specific invasive reaction assisted qPCR measure for ESR1 mutations in cfDNA. Two pivotal steps involved in this strategy are target-specific signal generation and the quantification without adding any internal reference or making standard calibration curves. The strategy enabled a high specificity of 0.1% (better than traditional NGS-based method) and a minimum sensitivity of 0.1 copies µL-1. As validation, with the strategy, cfDNA from endocrine therapy-resistant breast cancers and untreated ones were successfully analyzed (20% mutation rate (2/10) with mutation abundance of 0.54-1.65% vs. 0% mutation rate (0/5)). By virtue of cost-effective, highly flexible and precise, the strategy could be readily implemented in general laboratory, showing promising application perspectives in analysis of other types of mutations.

ZNF367-induced transcriptional activation of KIF15 accelerates the progression of breast cancer.

Breast cancer (BC) is one of the most common female cancers, and its incidence has been increasing in recent years. Although treatments are continuously improving, the prognosis of patients in the advanced stage is still unsatisfactory. Thus, an in-depth understanding of its molecular mechanisms is necessary for curing breast cancer. KIF15 is a tetrameric spindle motor which can regulate mitosis in cellular process and exert the crucial functions in several cancers. The purpose of our research was to investigate the functions of KIF15 in breast cancer. We tested the expression of KIF15 in breast cancer tissues and the survival rate of breast cancer patients with high or low level of KIF15 through TCGA data. What's more, western blot and immunohistochemistry assay were utilized to evaluate the protein level and mRNA level of KIF15 in breast cancer tissues. Then CCK-8, wound healing, transwell and flow cytometry experiments were adopted separately to test cell viability, migration, invasion and cell cycle distribution. We discovered that KIF15 was highly expressed in breast cancer tissues and high level KIF15 was associated with a low survival rate of breast cancer patients. Moreover, silence of KIF15 suppressed cell viability, migration, invasion and cell cycle distribution. Following, we discovered that ZNF367 was the upstream transcription factor of KIF15. In addition, silenced ZNF367 could also repress the growth of breast cancer cells. And rescue experiments indicated that overexpressed KIF15 could counteract the inhibition effect of silencing ZNF367 on the progression of breast cancer. Importantly, we discovered that KIF15 and ZNF367 were associated with the regulation of cell cycle. In short, ZNF367-activated KIF15 accelerated the progression of breast cancer by regulating cell cycle progress.

Overexpression of kinesin superfamily members as prognostic biomarkers of breast cancer.

BACKGROUND: Kinesin superfamily (KIFs) has a long-reported significant influence on the initiation, development, and progress of breast cancer. However, the prognostic value of whole family members was poorly done. Our study intends to demonstrate the value of kinesin superfamily members as prognostic biomarkers as well as a therapeutic target of breast cancer. METHODS: Comprehensive bioinformatics analyses were done using data from TCGA, GEO, METABRIC, and GTEx. LASSO regression was done to select tumor-related members. Nomogram was constructed to predict the overall survival (OS) of breast cancer patients. Expression profiles were testified by quantitative RT-PCR and immunohistochemistry. Transcription factor, GO and KEGG enrichments were done to explore regulatory mechanism and functions. RESULTS: A total of 20 differentially expressed KIFs were identified between breast cancer and normal tissue with 4 (KIF17, KIF26A, KIF7, KIFC3) downregulated and 16 (KIF10, KIF11, KIF14, KIF15, KIF18A, KIF18B, KIF20A, KIF20B, KIF22, KIF23, KIF24, KIF26B, KIF2C, KIF3B, KIF4A, KIFC1) overexpressed. Among which, 11 overexpressed KIFs (KIF10, KIF11, KIF14, KIF15, KIF18A, KIF18B, KIF20A, KIF23, KIF2C, KIF4A, KIFC1) significantly correlated with worse OS, relapse-free survival (RFS) and distant metastasis-free survival (DMFS) of breast cancer. A 6-KIFs-based risk score (KIF10, KIF15, KIF18A, KIF18B, KIF20A, KIF4A) was generated by LASSO regression with a nomogram validated an accurate predictive efficacy. Both mRNA and protein expression of KIFs are experimentally demonstrated upregulated in breast cancer patients. Msh Homeobox 1 (MSX1) was identified as transcription factors of KIFs in breast cancer. GO and KEGG enrichments revealed functions and pathways affected in breast cancer. CONCLUSION: Overexpression of tumor-related KIFs correlate with worse outcomes of breast cancer patients and can work as potential prognostic biomarkers.

KCTD12 promotes G1/S transition of breast cancer cell through activating the AKT/FOXO1 signaling.

BACKGROUND: Sustaining proliferation is the most fundamental step for breast cancer tumor genesis. Accelerated proliferation is usually linked to the uncontrolled cell cycle. However, the internal and external factors linked to the activation of breast cancer cell cycle are still to be investigated. METHODS: quantitative PCR (qPCR) and Western blotting assay were used to detect the expression of potassium channel tetramerization domain containing 12 (KCTD12) in breast cancer. MTT and colony formation assays were performed to evaluate the effect of KCTD12 on cell proliferation of breast cancer. Anchorage-independent growth assay was used to examine the in vitro tumorigenesis of breast cancer cells. Flow cytometry assay, qPCR, and Western blotting were used to investigate the detailed mechanisms of KCTD12 on breast cancer progression. RESULTS: Herein, the result showed that the level of KCTD12 is significantly decreased in breast cancer tissues and cells, and lower level of KCTD12 predicts poorer survival for patients with breast cancer. Further cell function tests illustrated that downregulation of KCTD12 significantly promotes cell proliferation and in vitro tumor genesis. Besides, molecular biologic experiments showed that downregulation of KCTD12 can enhance the G1/S transition through activating the AKT/FOXO1 signaling. CONCLUSION: Our study inferred that downregulation of KCTD12 can be a novel factor for poor prognosis in breast cancer.

HePTP promotes migration and invasion in triple-negative breast cancer cells via activation of Wnt/ß-catenin signaling.

AIM: Cancer metastasis remains a major challenge for the clinical management of breast cancer, especially triple-negative breast cancer (TNBC), and the underlying molecular mechanisms remain largely unknown. The aim of this study was to explore the mechanism of TNBC metastasis. MAIN METHODS: The expression of protein tyrosine phosphatase, non-receptor type 7 (HePTP) was detected using real time-PCR, western blot. Wound healing assay and transwell matrix assay were used to evaluate the pro-migration and pro-invasion potential of HePTP in vitro. Luciferase activity assay and nuclear extract analysis were used to evaluate Wnt/ß-catenin signaling activity. KEY FINDINGS: We reported that HePTP was overexpressed in TNBC, where it acted to drive migration and invasion of tumor cells. We showed that knockdown of HePTP significantly suppressed metastatic capacity of TNBC cells. Moreover, HePTP promoted cells migration and invasion by dephosphorylating glycogen synthase kinase 3 beta (GSK3ß), thereby activating Wnt/ß-catenin signaling. Additionally, we demonstrated that overexpression of HePTP in HePTP lowly expressed cells could effectively promote the migration and invasion of breast cancer cells. SIGNIFICANCE: Our results suggest that HePTP plays a key role in the metastasis of TNBC via activating Wnt/ß-catenin signaling. Hence, we propose that HePTP may serve as a novel prognostic marker and a potential therapeutic target for the treatment of TNBC.

ACE2 inhibits breast cancer angiogenesis via suppressing the VEGFa/VEGFR2/ERK pathway.

BACKGROUND: Breast cancer angiogenesis is key for metastasis and predicts a poor prognosis. Angiotensin-converting enzyme 2 (ACE2), as a member of the renin-angiotensin system (RAS), was reported to restrain the progression of hepatocellular carcinoma (HCC) and non-small cell lung cancer (NSCLC) through inhibiting angiogenesis. However, the relationship between ACE2 and breast cancer angiogenesis remains unclear. METHODS: The prognosis and relative gene selection were analysed using the GEPIA, GEO, TCGA and STRING databases. ACE2 expression in breast cancer tissue was estimated by reverse transcription-quantitative polymerase chain reaction (qPCR). Breast cancer cell migration, proliferation and angiogenesis were assessed by Transwell migration, proliferation, tube formation, and wound healing assays. The expression of vascular endothelial growth factor A (VEGFa) was detected by qPCR and Western blotting. The phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2), mitogen-activated protein kinase 1/2 (MEK1/2), and extracellular signal-regulated protein kinase 1/2 (ERK1/2) was examined by Western blotting. Breast cancer metastasis and angiogenesis in vivo were measured using a zebrafish model. RESULTS: ACE2 was downregulated in breast cancer patients. Patients with higher ACE2 expression had longer relapse-free survival (RFS). In vitro, ACE2 inhibited breast cancer migration. Meanwhile, ACE2 in breast cancer cells inhibited human umbilical vascular endothelial cell (HUVEC) proliferation, tube formation and migration. In the zebrafish model, ACE2 inhibited breast cancer cell metastasis, as demonstrated by analyses of the number of disseminated foci and the metastatic distance. Neo-angiogenesis was also decreased by ACE2. ACE2 downregulated the expression of VEGFa in breast cancer cells. Furthermore, ACE2 in breast cancer cells inactivated the phosphorylation of VEGFR2, MEK1/2, and ERK1/2 in HUVECs. CONCLUSIONS: Our findings suggest that ACE2, as a potential resister to breast cancer, might inhibit breast cancer angiogenesis through the VEGFa/VEGFR2/ERK pathway. TRIAL REGISTRATION: Retrospectively registered.

Downregulation of long non-coding RNA Opa interacting protein 5-antisense RNA 1 inhibits breast cancer progression by targeting sex-determining region Y-box 2 by microRNA-129-5p upregulation.

Several studies have shown an important role for long non-coding RNA (lncRNA) in breast cancer progression. The present study investigated the role of lncRNA Opa interacting protein 5-antisense RNA 1 (OIP5-AS1) in the progression of breast cancer. OIP5-AS1 was significantly upregulated in breast cancer tissues and in breast cancer cell lines, and OIP5-AS1 downregulation inhibited the malignant behavior of breast cancer in vitro and in vivo. For in-depth exploration of the mechanism of OIP5-AS1 in breast cancer, we found that expression of microRNA-129-5p(miR-129-5p), which was found to bind sites in the sequence of OIP5-AS1, in breast cancer tissues was negatively correlated with OIP5-AS1. Also, luciferase assays indicated that OIP5-AS1 acted as a miR-129-5p sponge, resulting in upregulated expression of the sex-determining region Y-box 2 (SOX2) transcription factor. Our study showed that OIP5-AS1 plays a critical role in promoting breast cancer progression and that OIP5-AS1 downregulation targets SOX2 by miR-129-5p upregulation.

microRNA-129-5p suppresses Adriamycin resistance in breast cancer by targeting SOX2.

Adriamycin resistance is closely related to therapeutic efficacy in breast cancer patients and their prognosis. Increasing evidence has suggested that miRNA functions in Adriamycin resistance in various types of cancer. microRNA-129-5p (miR-129-5p) has been considered a tumor-suppressive miRNA in several cancers, but its potential role in Adriamycin resistance in breast cancer has not been fully elucidate. By qRT-PCR assay, we revealed that the expression of miR-129-5p was significantly decreased in breast cancer tissues and Adriamycin-resistant breast cancer cells (MDA-MB-231/ADR, MCF-7/ADR). CCK-8, colony formation, wound healing, Transwell invasion, and flow cytometric profiles were examined to determine the influence of miR-129-5p on Adriamycin-resistant breast cancer in vitro. The upregulation of miR-129-5p decreased the IC50 concentration of Adriamycin and invasion and promoted the apoptosis of MDA-MB-231/ADR cells in the presence of Adriamycin, whereas the upregulation of Sex-Determining Region Y-Box 2 (SOX2) reversed these effects. A luciferase reporter assay confirmed the binding of miR-129-5p to the 3'UTR of SOX2. Collectively, it was suggested that miR-129-5p suppresses Adriamycin resistance in breast cancer by directly targeting SOX2.

MicroRNA-101 Inhibits Growth, Proliferation and Migration and Induces Apoptosis of Breast Cancer Cells by Targeting Sex-Determining Region Y-Box 2.

BACKGROUND: Increasing evidence has demonstrated that microRNAs play a critical role in breast cancer (BC) progression. microRNA-101 (miR-101) has been considered a tumor suppressive miRNA in different cancer types. This study aimed to investigate miR-101 expression in BC tissues and to investigate its roles in BC progression that are mediated by Sex-determining region Y-box 2 (SOX2), a critical oncogene in various cancers. METHODS: qRT-PCR and immunohistochemistry were performed to detect miR-101 and SOX2 expression in BC tissues and paired normal tissues or BC cell lines. MTT, transwell migration, wound healing, colony formation, flow cytometric and xenograft assays were performed to determine the influence of miR-101 and SOX2 on the malignant behaviors of BC cells in vitro and in vivo. RESULTS: miR-101 was significantly downregulated in BC tissues and cell lines. miR-101 overexpression inhibited the malignant behaviors of BC cells, both in vitro and in vivo. miR-101 downregulation had the converse effect. A miR-101 binding site was identified by luciferase reporter assay in the 3'UTR of SOX2. SOX2 was upregulated in BC tissues and cell lines, and its upregulation was associated with lymph node metastasis, pathological grade and TNM classification. SOX2 knockdown mimicked the effects of miR-101 overexpression on the malignant behaviors of BC cells, while SOX2 overexpression mitigated the miR-101-induced inhibition of these effects. CONCLUSIONS: Our study revealed that miR-101 plays a critical role in suppressing tumor progression by directly targeting SOX2.

Roles of sex-determining region Y-box 2 in cell pluripotency and tumor-related signaling pathways.

The sex-determining region Y-box 2 (SOX2) gene, a member of the Sry-like high-mobility group box (SOX) gene family, encodes the transcription factor Sox2, which significantly contributes to the regulation of cell pluripotency. Sox2 is closely associated with early embryonic development, neural differentiation and other biological processes. An inreasing number of recent studies suggest that Sox2 exerts a positive effect on malignant tumors. According to these results, Sox2 is expected to become a novel target for cancer therapy by unveiling the mechanism through which it affects the biological behavior of tumors. Therefore, it is crucial to elucidate the detailed association of Sox2 with malignant tumors. The aim of this study was to review the role of Sox2 in pluripotency maintenance, early embryonic development and neural differentiation, as well as investigate the detailed mechanism through which Sox2 regulates cancer stem cells and tumorigenesis.

Study of yellow luminescence of binary terbium complexes based on 3,3',4,4'-biphthalic anhydride.

Three novel binary Tb(III) complexes (TbL2, TbL, and Tb2L; L=3,3',4,4'-biphenyl tetracarboxylic ligand) were synthesized by changing the molar ratio of Tb(III) to 3,3',4,4'-biphthalic anhydride (BPDA) (1∶2, 1∶1, and 2∶1, respectively). IR spectra indicate that there are two coordination modes of the carboxylate ligands with Tb3+ ions in the complexes. Most of them are in bridging mode; the others are in chelating mode. These complexes all have good thermal stability. The photophysical properties of these complexes are studied in detail using UV absorption spectra, fluorescence spectra, and transient fluorescence spectra. The results indicate that the photoluminescence properties of the complexes depend strongly on the molar ratio of Tb(III) to BPDA. When the molar ratio of Tb(III) to BPDA is 1∶1, complex TbL exhibits the strongest yellow light emission among the three Tb(III) complexes. However, complex Tb2L exhibits a weaker yellowish-green light emission when the molar ratio of Tb(III) to BPDA is 2∶1. The phenomenon of the yellow emission from terbium complexes is rarely reported.

Microcystin (-LR) induced testicular cell apoptosis via up-regulating apoptosis-related genes in vivo.

Microcystin-LR (MC-LR) can induce apoptosis of a wide range of tissue cells including testicular cells. The purpose of the study was to find out whether the expression and phosphorylation of p53, Bcl-2 protein family proteins, Cyt c, and caspases were involved in the induction of testicular cell apoptosis by MC-LR in mice. Results showed that following exposure to MC-LR, expression of Bax, caspase 3 and caspase 8 was up-regulated. Significant increases in the phosphorylation of both p53 and Bcl-2 were identified after the administration of MC-LR. The administration of MC-LR also resulted in significant increases of c-myc, c-jun, and c-fos. In conclusion, p53, Bcl-2, Bax, Caspase 3 and Caspase 8 are involved in the regulation of MC-LR-induced apoptosis of testicular cells. The overexpression of c-myc, c-jun and c-fos suggests that MC-LR may have carcinogenic potential for testes.