Lnc-CLSTN2-1:1 Promotes Osteosarcoma Progression by Disrupting Redox Balance through PI3K/AKT Signaling Pathway.

Objective: Most patients with osteosarcoma (OS) have an extremely poor prognosis. The primary purpose of this investigation was to explore the biological effect of Lnc-CLSTN2-1:1 on OS and the potential processes involved. Materials and procedures: We selected differentially overexpressed Lnc-CLSTN2-1:1 from our laboratory's existing RNA sequence analysis data (fibroblast osteoblast (hFOB 1.19) and three osteosarcoma cell lines (HOS, MG63, and U2OS) as the research object. Next, we detected Lnc-CLSTN2-1:1 in the osteosarcoma HOS cell line and fibroblast cells using qRT-PCR. We evaluated cell proliferation ability using EdU incorporation test, CCK-8 test, and cell clone formation; cell invasion and migration were assessed using the Transwell test, while flow cytometry examined cell cycle, apoptosis, and reactive oxygen species (ROS); Subsequently, the activity changes of selenase (GPx) glutathione peroxidase and (TrxR) thioredoxin reductase were detected. In addition, changes in related proteins were analyzed through Western blotting. Results: The expression of Lnc-CLSTN2-1:1 in osteosarcoma cells was significantly increased. The proliferation, invasion, and migration of osteosarcoma cells were significantly inhibited by knockdown of the expression of Lnc-CLSTN2-1:1, and the cell cycle-related signaling pathway PI3K/AKT/GSK-3ß/cycinD1 was also inhibited. However, insulin-like growth factor-1 (igf-1) could reverse this process. In addition, we examined the activity of two selenophenases (TrxR and GPx) and the changes of ROS before and after Lnc-CLSTN2-1:1 knockdown. The results showed that both TrxR and GPx activities were reduced after Lnc-CLSTN2-1:1 knockdown, resulting in the inhibition of antioxidant stress levels, while intracellular ROS levels were high, which eventually caused killing effects on tumor cells due to the imbalance between oxidative stress and antioxidant stress. Conclusion: Our results showed that Lnc-CLSTN2-1:1 enhanced anti-oxidative stress TrxR and GPx selenoprotein activities through the PI3K/AKT signaling pathway while counteracting the loss of reactive oxygen species ROS produced by mitochondria to osteosarcoma cells, which protected osteosarcoma cells and thus promoted the proliferation and metastatic ability of OS.

Genetic alterations of KRAS and TP53 in intrahepatic cholangiocarcinoma associated with poor prognosis.

The aim of this study is to investigate certain genetic features of intrahepatic cholangiocarcinoma (ICCA). A total of 12 eligible ICCA patients were enrolled, and tumor tissues from the patients were subjected to next-generation sequencing of a multi-genes panel. Tumor mutation burden (TMB), mutated genes, copy number variants (CNVs), and pathway enrichment analysis were performed. The median TMB was 2.76 Mutation/Mb (range, 0-36.62 Mutation/Mb) in ICCA patients. The top two most commonly mutated genes in ICCA were KRAS (33%) and TP53 (25%). The co-mutations of KRAS and TP53 were 16.7% (2/12) in ICCA patients. Notably, patient P6 with the highest TMB did not have KRAS and TP53 mutations. Additionally, TP53 and/or KRAS alterations were significantly associated with poor progression-free survival than those with wild type (1.4 months vs 18 months). DNA damage repair and homologs recombinant repair deficiencies were significantly associated with high TMB in ICCA cases. In conclusion, we found that certain genetic mutations of TP53 and KRAS could predict poor prognosis in ICCA patients.

hsa_circ_0136839 regulates the malignant phenotypes of nasopharyngeal carcinoma via the Wnt/ß-catenin signaling pathway.

With the development of RNA sequencing (RNA-seq) technology, circular RNA (circRNA), a new class of RNA, has received much attention in cancer research. However, information available on the biogenesis and functional value of circRNAs in nasopharyngeal carcinoma (NPC) is scarce. In the present study, we screened the circRNA profile of the NPC cell line C666-1 compared with that of the normal control NP69 by RNA-seq and identified a novel and relatively higher expressed circRNA, hsa_circ_0136839. Hsa_circ_0136839 was markedly downregulated in NPC tissues, as confirmed by quantitative reverse transcription polymerase chain reaction. Functional in vitro studies revealed that hsa_circ_0136839 knockdown in C666-1 cell notably promoted cell proliferation, migration, and invasion abilities, as well as affected cell cycle distribution with an S-phase arrest. However, hsa_circ_0136839 overexpression in CNE2 cells resulted in an opposite response. Mechanistically, we demonstrated that aberrant hsa_circ_0136839 expression might affect the malignant phenotypes of NPC cells by activating the wnt/ß-catenin signaling pathway. Thus, our findings contribute to further the understanding of NPC pathogenesis and provide new ideas for NPC clinical diagnosis and treatment.

Hsa_circ_0087302, a circular RNA, affects the progression of osteosarcoma via the Wnt/ß-catenin signaling pathway.

Osteosarcoma is the most common malignant tumor in adolescent bone malignancies. It has the characteristics of a high metastasis rate, high mortality and poor prognosis. As a subclass of endogenous noncoding RNAs, circRNAs have been identified to be related to the occurrence, development and prognosis of different kinds of cancers, but the mechanism of their effect on osteosarcoma is not clear. In the present study, we identified a novel circRNA, hsa_circ_0087302, by RNA-seq, and we found that it was expressed at low levels in osteosarcoma. Using RT-PCR, we confirmed that the expression of hsa_circ_0087302 in osteosarcoma cells was lower than that in osteoblasts. Functional validation experiments revealed that hsa_circ_0087302 overexpression inhibited proliferation, cell cycle, migration, and invasion in osteosarcoma cells. Furthermore, Western blotting experiments demonstrated that hsa_circ_0087302 affected the expression of cell cycle- and Wnt/ß-catenin signaling pathway-related proteins. For the first time, we identified that hsa_circ_0087302 may affect the malignant biological behavior of osteosarcoma cells through the Wnt/ß-catenin signaling pathway. In summary, hsa_circ_0087302 may provide a new direction for the diagnosis and treatment of osteosarcoma.

Lnc-MAP6-1:3 knockdown inhibits osteosarcoma progression by modulating Bax/Bcl-2 and Wnt/ß-catenin pathways.

Osteosarcoma (OS) is the most common type of malignant bone tumor that affects children and adolescents. Still, the cellular and molecular mechanisms driving the development of this disease remain poorly understood. In this study, numerous dysregulated lncRNAs were identified by RNA-seq. As a result, we were able to find a novel lncRNA Lnc-MAP6-1:3 which is highly expressed in osteosarcoma. Using a set of approaches including gene knockdown, RT-PCR, oncogenic function assay and western blotting, we observed that knockdown of Lnc-MAP6-1:3 expression suppressed cell proliferation and colony formation, and promoted apoptosis in vitro. For the first time, we have identified that Lnc-MAP6-1:3 potentially influence the malignant behavior of osteosarcoma via Bax/Bcl-2 and Wnt/ß-catenin signaling pathways. Henceforth, Lnc-MAP6-1:3 may provide a new molecular route of research and therapeutic applications for the diagnosis and treatment of osteosarcoma.

Contemporary Chinese centenarians: Health profiles, social support and relationships in Suixi County.

BACKGROUND: Centenarians are the fastest growing population worldwide. However, this group has been less studied in developing countries. Contemporary centenarians in China have experienced many ups and downs due to historical reasons, which may have resulted in a population with different characteristics from those in other countries. This study aimed to investigate the current sociodemographic characteristics, health profiles, and social relationships of Chinese centenarians. METHODS: We conducted face-to-face surveys in April 2017 with centenarian residents in Suixi County, the first "International Healthy Longevity Area" in China. A total of 100 centenarians were involved, including 67 females and 33 males. Information for socioeconomic and demographics characteristics, quality of life (physical, cognitive, and psychological function), and social support and relationships was collected. Sex differences in each measure were examined. RESULTS: We find that good self-reported health, good life satisfaction, intact memory function, independence, and unsatisfied healthcare needs were reported by 24.4%, 45.9%, 31.6%, 46.3%, and 33.4% of the respondents respectively. Subjective symptoms among males were less prevalent (p < 0.05). There were no statistical significant sex differences in cognitive and psychological function. The major source of care provision has been family. Generally, the centenarians had intimate relationships within families but maintained distant relationships with friends and communities. CONCLUSION: Our results bring attention to family-based care to provide informal care, and health education to promote healthy behaviors and healthcare utilization, for the oldest-old in China. The findings also imply a crucial role of good relationships with family in exceptional longevity.

Highly Uniform Synthesis of Selenium Nanoparticles with EGFR Targeting and Tumor Microenvironment-Responsive Ability for Simultaneous Diagnosis and Therapy of Nasopharyngeal Carcinoma.

Rational design of multifunctional and smart drug-delivered nanoplatforms is a promising strategy to achieve simultaneous diagnosis, real-time monitoring, and therapy of cancers. Herein, highly uniform and stable selenium nanoparticles with epidermal growth factor receptor (EGFR) targeting and tumor microenvironment-responsive ability (Se-5Fu-Gd-P(Cet/YI-12)) were designed and synthesized by using EGFR as the targeting molecule, gadolinium chelate as the magnetic resonance imaging contrast agent, 5-fluorouracil (5Fu) and cetuximab as drug payloads, polyamidoamine (PAMAM) and 3,3'-dithiobis (sulfosuccinimidyl propionate) as the response agents of intratumoral glutathione, and pH for the treatment and diagnosis of nasopharyngeal carcinoma (NPC). This Se nanoplatform showed excellent magnetic resonance imaging capability and has the potential for its clinical application as a diagnostic agent for tumor tissue specimens. Additionally, in vitro cellular experiments showed that by means of introducing clinical targeted drugs and peptides not only validly increased the intracellular uptake of the Se nanoplatform in NPC cells but also enhanced its penetration ability toward CNE tumor spheroids, resulting in simultaneous inhibition of CNE cell growth, invasion, and migration. In addition, the sequentially triggered bioresponsive property of the nanoplatform in a tumor microenvironment effectively improved the targeting delivery and anticancer efficiency of payloads. Overall, this study not only provides a strategy for facile synthesis of highly uniform and stable nanomedicines and tailing of the bioresponsive property but also sheds light on its application in targeting theranosis of NPC.

Structure-Activity Relationship Analysis on Antioxidant and Anticancer Actions of Theaflavins on Human Colon Cancer Cells.

The roles of natural products as effective cancer prevention and therapeutic agents have been documented by various studies in recent years, but the action mechanisms and structure-activity relationship need more elucidation. The present study showed that theaflavins (theaflavin and its derivatives, TFs) from black tea caused an inhibitory effect on the proliferation of human colon adenocarcinoma cancer SW480 cells and human colon cancer SW620 cells [half maximal inhibitory concentration (IC50) < 32.0 µM] by the induction of cell cycle arrest but exerted lower toxicity against normal cells with a high safety index (1.89-6.26). Moreover, TFs triggered a decrease in reactive oxygen species in SW480 cells as a result of their excellent radical-scavenging ability (e.g., the IC50 value of TF4 to ABTS• + was 1.91 ± 0.21 µM). More importantly, the structure-activity relationship analysis of TFs exhibited that the galloyl group was an important factor to affect these activities. Taken together, we revealed that the TFs could act as substitutes for natural antioxidants and promising anticancer agents with beneficial influence on human health and then anticipated that this study may provide useful information on the development of therapeutic natural products.

Enhanced expression of SETDB1 possesses prognostic value and promotes cell proliferation, migration and invasion in nasopharyngeal carcinoma.

SETDB1, an H3K9­specific histone methyltransferase, has been described as a repressed transcription marker which triggers tumorigenesis of many types of human cancer. However, there are few studies elucidating the relationship between SETDB1 and nasopharyngeal carcinoma. In the present study, we confirmed that SETDB1 exhibited higher expression levels in nasopharyngeal carcinoma (NPC) tissues and cell lines, compared to these levels in non­tumor tissues and a normal human nasopharyngeal epithelial cell line. Kaplan­Meier analysis showed that higher SETDB1 expression indicated an unfavorable prognosis for NPC patients, making it an independent prognostic factor for NPC in the COX proportional hazards model. In vitro functional studies revealed that upregulation of SETDB1 expression in CNE1 cells promoted cell proliferation, possibly through cell cycle G1/S phase transition. Moreover, it also enhanced cell migration and invasion ability. Downregulation of SETDB1 expression in 5­8F cells resulted in the opposite response. Overall, the findings indicated that increased expression of SETDB1 may predict poor overall survival and the malignant phenotype of NPC.

Fatty Acid Binding Protein 11a Is Required for Brain Vessel Integrity in Zebrafish.

The monolayer of endothelial cells (ECs) lining the intima of all blood vessel wall forms a semipermeable barrier that regulates tissue-fluid homeostasis, transport of nutrients, and migration of blood cells across the barrier. A number of signaling pathways and molecules mediate endothelial permeability, which plays important roles in a variety of the physiological and pathological conditions. Fatty acid binding proteins (FABPs) are able to bind various hydrophobic molecules, such as long-chain fatty acids, prostaglandins and eicosanoids. FABP4, a member of the family of FABPs, plays an important role in maintenance of glucose and lipid homeostasis as well as angiogenesis. In the present study, we found that fabp11a, the ortholog of mammalian FABP4, was highly expressed in developing brain vessels of zebrafish. Knockout of fabp11a gene caused hemorrhage in zebrafish brain. Morpholino mediated fabp11a gene knockdown phenocopied the hemorrhage in mutants. Furthermore, we demonstrated permeability of brain vessels in fabp11a mutant is significantly higher than that of control. In addition, COX and LOX inhibition partially rescued the brain vessel integrity defects caused by fabp11a loss-of-function, suggesting the integrity defect was relevant to the Fatty Acid function.