ABSTRACT
A substantial fraction of eukaryotic transcripts are considered long non-coding RNAs (lncRNAs), which regulate various hallmarks of cancer. Here, we discovered that the lncRNA HOXB-AS3 encodes a conserved 53-aa peptide. The HOXB-AS3 peptide, not lncRNA, suppresses colon cancer (CRC) growth. Mechanistically, the HOXB-AS3 peptide competitively binds to the ariginine residues in RGG motif of hnRNP A1 and antagonizes the hnRNP A1-mediated regulation of pyruvate kinase M (PKM) splicing by blocking the binding of the ariginine residues in RGG motif of hnRNP A1 to the sequences flanking PKM exon 9, ensuring the formation of lower PKM2 and suppressing glucose metabolism reprogramming. CRC patients with low levels of HOXB-AS3 peptide have poorer prognoses. Our study indicates that the loss of HOXB-AS3 peptide is a critical oncogenic event in CRC metabolic reprogramming. Our findings uncover a complex regulatory mechanism of cancer metabolism reprogramming orchestrated by a peptide encoded by an lncRNA.
Subject(s)
Cell Transformation, Neoplastic/genetics , Colonic Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Heterogeneous-Nuclear Ribonucleoprotein Group A-B/genetics , Peptides/genetics , RNA, Long Noncoding/genetics , Alternative Splicing , Amino Acid Motifs , Animals , Binding, Competitive , Cell Line, Tumor , Cell Transformation, Neoplastic/metabolism , Cell Transformation, Neoplastic/pathology , Colonic Neoplasms/metabolism , Colonic Neoplasms/pathology , Exons , HeLa Cells , Heterogeneous Nuclear Ribonucleoprotein A1 , Heterogeneous-Nuclear Ribonucleoprotein Group A-B/metabolism , Heterografts , Humans , Mice , Mice, Inbred NOD , Mice, SCID , Peptides/antagonists & inhibitors , Peptides/metabolism , Protein Binding , Protein Interaction Mapping , Pyruvate Kinase/genetics , Pyruvate Kinase/metabolism , RNA, Long Noncoding/antagonists & inhibitors , RNA, Long Noncoding/metabolism , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Signal TransductionABSTRACT
OBJECTIVE: To investigate the impact of cigarette smoking on sperm nucleoprotein transition and its association with sperm motility in infertile males. METHODS: We examined the semen quality and sperm nucleoprotein transition of 116 non-smokers and 113 heavy smokers (aged 25 -50 years) who visited the Research Institute of Obstetrics and Gynecology for male infertility. We determined the rate of individual sperm nucleoprotein transition by aniline blue staining and analyzed the correlation of cigarette smoking with routine semen parameters and the rate of sperm nucleoprotein transition. Based on the smoking index (SI) derived from smoking frequency (no. of cigarettes/d) multiplied by smoking duration (yr), the men with SI = 0 were considered as non-smokers, and those with SI > or = 200 as heavy smokers. RESULTS: The rate of abnormal sperm nucleoprotein transition was significantly higher in the asthenozoospermic (23.5 +/- 9.4, P < 0.01) and oligoasthenozoospermic (28.2 +/- 9.2, P < 0.01) than in the normozoospermic males (19.0 +/- 9.0). Compared with the non-smokers, cigarette smoking remarkably reduced sperm nucleoprotein transition in both the men with normal sperm motility (21.9 +/- 9.8 vs 16.8 +/- 7.7, P < 0.01) and those with abnormal sperm motility (26.0 +/- 9.9 vs 22.7 +/- 8.8, P < 0.05). A weak correlation was observed between the rate of sperm nucleoprotein transition and routine semen parameters. CONCLUSION: Cigarette smoking is not significantly correlated with sperm motility but decreases sperm nucleoprotein transition in infertile males.
Subject(s)
Infertility, Male/metabolism , Nucleoproteins/metabolism , Smoking/adverse effects , Spermatozoa/pathology , Adult , Humans , Male , Middle Aged , Sperm Motility/drug effectsABSTRACT
OBJECTIVE: To investigate the diagnosis and treatment of male Kallmann syndrome. METHODS: We retrospectively analyzed the clinical data of 12 cases of male Kallmann syndrome, 3 treated for male sterility and the other 9 for secondary sex characteristics dysplasia and external genitalia developmental anomalies, all by combined replacement therapy with human chorionic gonadotropin (hCG), human menopause gonadotropin (hMG) and testosterone undecanoate for 6 months to 3 years. We compared the secondary sexual development and serum sex hormone levels of the patients before and after treatment. RESULTS: After 9 months of treatment, all the 12 patients showed significant improvement in the penile length, testicular volume and sex hormone levels (P < 0.01), with different degrees of promotion of the secondary sexual development. Three married cases could have normal sexual intercourse, and one of them achieved normal pregnancy. CONCLUSION: The clinical characteristics of Kallmann syndrome include lack of gonadotropins, lower gonad function and loss or reduction of olfactory sensation. Replacement therapy with hCG, hMG and androgens is an effective treatment method. However, no effective therapy is now available for olfactory dysfunction. Early diagnosis and hormone replacement therapy can best alleviate its clinical symptoms and eventually achieve fertility.
Subject(s)
Hormone Replacement Therapy , Kallmann Syndrome/diagnosis , Kallmann Syndrome/drug therapy , Adolescent , Adult , Humans , Male , Retrospective Studies , Young AdultABSTRACT
BACKGROUND: Many studies have investigated the association between glutathione S-transferase T 1 (GSTT1) null genotype and risk of prostate cancer, but the impact of GSTT1 null genotype in Asians is still unclear owing to inconsistencies across results. Thie present meta-analysis aimed to quantify the strength of the association between GSTT1 null genotype and risk of prostate cancer. METHODS: We searched the PubMed, Embase and Wangfang databases for studies of associations between the GSTT1 null genotype and risk of prostate cancer in Asians and estimated summary odds ratio (OR) with their 95% confidence interval (95% CI). RESULTS: A total of 11 case-control studies with 3,118 subjects were included in this meta-analysis, which showed the GSTT1 null genotype to be significantly associated with increased risk of prostate cancer in Asians (random-effects OR = 1.49, 95% CI 1.15-1.92, P = 0.002), also after adjustment for heterogeneity (fixed-effects OR = 1.45, 95% CI 1.23-1.70, P< 0.001). No evidence of publication bias was observed. CONCLUSIONS: This meta-analysis of available data suggested the GSTT1 null genotype does contribute to increased risk of prostate cancer in Asians.
Subject(s)
Genetic Predisposition to Disease , Glutathione Transferase/genetics , Prostatic Neoplasms/genetics , Asia , Asian People/genetics , Case-Control Studies , Genotype , Glutathione Transferase/deficiency , Humans , Male , Risk FactorsABSTRACT
OBJECTIVE: To explore the correlation of the testosterone level with circulated endothelial progenitor cells in patients with Klinefelter's syndrome (KS) and its clinical significance. METHODS: This study included 36 patients affected by non-mosaic 47, XXY KS, each with one or more cardiovascular risk factors. Serum hormone levels and the content of circulated endothelial progenitor cells were determined by radioimmunology and cell culture methods, respectively, and the measurement was repeated after 6 months of testosterone replacement therapy. RESULTS: After testosterone replacement therapy, the testosterone level was increased from (8 +/- 3) to (24 +/- 10) nmol/L, while the content of endothelial progenitor cells ([41 +/- 48] cells/ml) showed no significant rise. CONCLUSION: There is no obvious correlation between the testosterone level and the content of endothelial progenitor cells in KS patients.
