LncRNA INHBA-AS1 promotes colorectal cancer cell proliferation by sponging miR-422a to increase AKT1 axis.

OBJECTIVE: In recent years, long non-coding RNAs (lncRNAs) have emerged for regulating the development, as well as progression in colorectal cancer (CRC), which assists in finding new targets for CRC treatment. A previous study indicated that INHBA-AS1 promotes oral squamous cell progression by sponging miR-143-3p. However, the exact function possessed by lncRNA INHBA-AS1 in CRC development remains unclear. PATIENTS AND METHODS: The expression level of INHBA-AS1 in CRC tissues and cell lines was determined by qRT-PCR. The functional role of INHBA-AS1 in CRC was investigated by a series of in vitro assays. RNA immunoprecipitation (RIP), bioinformatics analysis was utilized to explore the potential mechanisms of INHBA-AS1. RESULTS: The present study identified INHBA-AS1 as a kind of lncRNA with high expression in CRC tissues and cells. Functionally, NHBA-AS1 downregulation in CRC cells suppressed CRC cell proliferation as well as colony formability. Mechanistically, INHBA-AS1/miR-422a/AKT1 established the ceRNA network to regulate MMP-2, -7, -9 expressions that participated the modulation of CRC progression. CONCLUSIONS: In summary, LncRNA INHBA-AS1 contributes to CRC progression through AKT1 pathway, and provides a new mechanism to regulate CRC development, as well as a potential target for treating CRC.

SPAG5 promotes proliferation and suppresses apoptosis in bladder urothelial carcinoma by upregulating Wnt3 via activating the AKT/mTOR pathway and predicts poorer survival.

Sperm-associated antigen 5 (SPAG5) is involved in various biological processes. However, the roles of SPAG5 in bladder urothelial carcinoma (BUC) are unknown. This study showed that upregulation of SPAG5 was detected frequently in primary BUC tissues, and was associated with significantly worse survival among the 112 patients that underwent radical cystectomy (RC). Up and downregulating the expression of SPAG5 enhanced or inhibited, respectively, the proliferation of BUC cells in vitro and in vivo, and suppressed or enhanced, respectively, apoptosis in vitro and in vivo. Moreover, SPAG5 increased the resistance of BUC cells to chemotherapy-induced apoptosis. Mechanistic investigations showed that SPAG5 promotes proliferation and suppresses apoptosis in BUC at least partially via upregulating Wnt3 through activating the AKT/mTOR signaling pathway. The importance of the SPAG5/AKT-mTOR/Wnt3 axis identified in BUC cell models was confirmed via immunohistochemical analysis of a cohort of human BUC specimens that underwent RC. Collectively, our data suggested that in patients with BUC who underwent RC, high SPAG5 expression is associated with poor survival. In addition, targeting SPAG5 might represent a novel therapeutic strategy to improve the survival of patients with BUC.

Impact Factors and Attitudes Toward Organ Donation Among Transplantation Patients and Their Caregivers in China.

PURPOSE: This study's purpose was to investigate the attitudes toward organ donation among renal transplantation patients and their caregivers. In addition, we sought to explore the impact factors that affect their attitudes toward deceased organ donation. DESIGN AND METHODS: A self-administrated questionnaire was used, which consisted of two parts: 1) demographic data, and 2) transplantation and donation-related data. This study was conducted in three transplantation follow-up centers in three hospitals using a cross-sectional approach. SPSS 17.0 software was used to analysis descriptive and inferential statistics for data. The responses were analyzed using descriptive statistics and logistic regression analysis. RESULTS: We received 426 effective questionnaires. The renal transplantation patients' mean age was 40.84 years. Among these patients, 67.8% were willing to accept the organ transplantation surgery for their relatives, 67.4% were willing to donate a living kidney to a close relative, 62.7% were willing to donate organs after death, 53.5% were willing to register in the national organ donation system, and 51.4% were willing to sign the organ donation consent when facing their relatives becoming a potential organ donor. Age, marriage status, education level, understanding of transplantation procedures and understanding of donation procedures had statistical significance in the difference of the attitudes toward donate their organs after death (P < .05). CONCLUSIONS: Renal transplantation patients in our study are more willing to donate organs after death than their caregivers, but both their attitudes toward deceased donation were not very optimistic. There is a significant relationship between participants' willingness and knowledge of organ donation; patients with more understanding of the transplantation and donation procedure were more willing to donate organs after death. Affected by traditional values such as Confucianism, many people still cannot accept registering in the national organ donation system or sign the organ donation consent when facing their relatives becoming potential organ donors. CLINICAL RELEVANCE: There is a need to give adequate training regarding donation to increase donation rates. The government must provide education from the perspective of scientific knowledge to change the traditional views of the public, which may then increase the donation rate in China.

Low miR-34c expression is associated with poor outcome in de novo acute myeloid leukemia.

INTRODUCTION: MicroRNA-34c (miR-34c) has been found to play important roles in tumorigenesis. However, little is known about miR-34c expression and the impact on prognosis in acute myeloid leukemia (AML). METHODS: Real-time quantitative PCR (qRT-PCR) was performed to analyze the status of miR-34c expression in 122 patients with de novo AML and 62 normal controls. RESULTS: MiR-34c expression in AML was significantly downregulated compared to controls (P < 0.001). Receiver operating characteristic curves (ROC) indicated the distinguishing value of miR-34c for discriminating whole-cohort AML, non-M3 AML, and cytogenetically normal AML (CN-AML) patients from healthy controls. No significant differences were found between low miR-34c-expressing and high miR-34c-expressing patients in age, sex, hemoglobin, platelet count, percentage of blasts in bone marrow (BM), WHO classifications, karyotypes, and eight gene mutations, but low miR-34c cases had higher white blood cells (WBC) than high miR-34c cases (P = 0.035). MiR-34c low-expressed patients had similar rates of complete remission (CR) as miR-34c high-expressed patients in whole-cohort AML, non-M3 AML, and CN-AML patients (P = 0.347, 0.314 and 0.167, respectively). Kaplan-Meier analysis indicated that patients with low miR-34c level had markedly shorter overall survival (OS) time in whole-cohort AML, non-M3 AML, and CN-AML patients (P = 0.033, 0.024 and 0.001, respectively). Furthermore, multivariate analysis confirmed that low miR-34c expression was an independent risk factor not only in whole-cohort AML (P = 0.040) but also in non-M3 AML (P = 0.015) and CN-AML patients (P = 0.021). CONCLUSIONS: Our findings indicate that low miR-34c level is a novel promising biomarker in predicting prognosis in patients with de novo AML.

Association between the 8q24 rs6983267 T/G polymorphism and prostate cancer risk: a meta-analysis.

Recent studies have indicated that single nucleotide polymorphisms (SNPs) within the 8q24 region may be a risk factor for prostate cancer (PCa). Here, we performed a meta-analysis to evaluate the association between the 8q24 rs6983267 T/G polymorphism and PCa risk. A systematic literature search was carried out in multiple electronic databases independently by two investigators. Pooled odds ratios (ORs) and 95% confidence intervals for 8q24 rs6983267 T/G and PCa were calculated using a fixed-effect model (the Mantel-Haenszel method). In total, 24 case-control studies from 19 articles were included in our meta-analysis. Our analysis indicated that there is a significant PCa risk associated with the rs6983267 polymorphism in a dominant model (GG vs GT+TT, pooled OR = 1.298, P < 0.001); recessive model (GG+GT vs TT, pooled OR = 1.302, P < 0.001); and homozygote comparison (GG vs TT, pooled OR = 1.494, P < 0.001). Similarly, in a subgroup analysis of European and Asian descent, our results revealed that there are associations between rs6983267 T/G polymorphism and PCa susceptibility with the dominant model (GG vs GT+TT), recessive model (GG+GT vs TT), and homozygote comparison (GG vs TT). To investigate the association between rs6983267 and risk of PCa under different clinical conditions, further analyses were conducted regarding different clinical characteristics including the Gleason score, tumor stage, and PSA level to provide a more comprehensive view of PCa risk and this SNP. Publication bias was assed using the Begg test and the Egger test, and none was detected.

Genetic association of tumor necrosis factor-ß, interleukin-10, and interleukin-1 gene cluster polymorphism with susceptibility to pneumonia in kidney transplant recipients.

INTRODUCTION: Pneumonia remains a significant cause of morbidity and mortality after kidney transplantation. The present study was therefore conducted to investigate whether or not the polymorphisms of tumor necrosis factor (TNF)ß, interleukin (IL)-10, IL-1ß, and IL-1 receptor antagonist (IL-1ra) gene predicted the susceptibility to pneumonia within the first year after kidney transplantation. METHODS: Subjects comprised 33 kidney transplant recipients with pneumonia and 63 noninfected kidney transplant recipients. Genomic DNA from these 96 kidney transplant recipients was extracted from peripheral blood leukocytes. The regions containing the NcoI polymorphic site at position +252 of TNFß gene, the RsaI polymorphic site at position -592 of IL-10 gene, and the AvaI polymorphic site at position -511 of IL-1ß gene were amplified by polymerase chain reaction (PCR) and subsequently digested with NcoI, RsaI, and AvaI restriction enzyme, respectively. The polymorphic regions with intron 2 of the IL-1 ra gene (IL-1 RN) containing variable numbers of a tandem repeat of 86 base pairs, were amplified by PCR. RESULTS: Univariate analysis showed that recipient IL-10, IL-1ß, and IL-1 RN polymorphisms were not associated with the presence of pneumonia (P = .589, .940, and .286, respectively). However, compared with GG genotype, recipient TNFß +252AA + AG genotype was significantly associated with susceptibility to pneumonia (P = .006). Age of 45 years or older was not significantly associated with susceptibility to develop pneumonia but had a tendency to develop it (P = .119). After adjusting for age of 45 years or older, recipient TNFß+252 AA + AG genotype (odds ratio = 5.366, 95% confidence intervals = 1.470 - 19.589, P = .011) independently predicted the risk for pneumonia within the first year after kidney transplantation in the multivariate analysis. CONCLUSION: These results suggested that recipient TNFß gene polymorphism may be useful in predicting pneumonia, hence identifying individuals who could benefit from preventive treatment and a less potent immunosuppression regimen.

Umbilical cord blood lead levels in Shanghai, China.

This study was designed to determine the cord blood lead (BPb) levels of babies born in one urban area of Shanghai, and to preliminarily identify the demographic, social environment and prenatal factors which have an effect on the cord BPb concentrations. From August to November 1993, umbilical cord blood samples were obtained from 605 live newborns in the Yangpu Maternal and Child Hospital. 257 samples were excluded from measurement because of clotting. In 348 cord samples, the geometric mean of cord BPb levels was 9.2 micrograms/dl, with a 95% confidence interval of the mean 8.86-9.54 (micrograms/dl). 142 babies (40.8%) had cord BPb levels of 10 micrograms/dl or greater. As a result of this high percentage of newborns with BPb levels equal to or greater than 10 micrograms/dl, we estimate that each year in the Shanghai City about 60,000 newborns are at risk for developing neuropsychological deficiencies caused by maternal lead exposure during pregnancy. To investigate the factors affecting cord blood levels, the subjects with levels greater than the 70th percentile (10.7 micrograms/dl) (n = 104) and less than the 30th percentile (7.4 micrograms/dl) (n = 104) were selected to compare the demographic, environment and prenatal medical history. Increased BPb levels at birth were associated with maternal passive smoking, a family member being occupationally exposed to lead, proximity to major traffic way, household coal combustion, neighborhood coal combustion, low level of maternal occupations, and the increasing occurrence of having the high lead foodstuff pidan (preserved duck egg) during pregnancy. We conclude that prenatal lead exposure has become an important health issue for young children in Shanghai.