ABSTRACT
The insulin-like growth factors (IGFs) and their regulatory proteins-IGF receptors and binding proteins-are strongly implicated in cancer progression and modulate cell survival and proliferation, migration, angiogenesis and metastasis. By regulating the bioavailability of the type-1 IGF receptor (IGF1R) ligands, IGF-1 and IGF-2, the IGF binding proteins (IGFBP-1 to -6) play essential roles in cancer progression. IGFBPs also influence cell communications through pathways that are independent of IGF1R activation. Noncoding RNAs (ncRNAs), which encompass a variety of RNA types including microRNAs (miRNAs) and long-noncoding RNAs (lncRNAs), have roles in multiple oncogenic pathways, but their many points of intersection with IGF axis functions remain to be fully explored. This review examines the functional interactions of miRNAs and lncRNAs with IGFs and their binding proteins in cancer, and reveals how the IGF axis may mediate ncRNA actions that promote or suppress cancer. A better understanding of the links between ncRNA and IGF pathways may suggest new avenues for prognosis and therapeutic intervention in cancer. Further, by exploring examples of intersecting ncRNA-IGF pathways in non-cancer conditions, it is proposed that new opportunities for future discovery in cancer control may be generated.
Subject(s)
MicroRNAs , Neoplasms , RNA, Long Noncoding , Humans , Insulin-Like Growth Factor Binding Proteins/genetics , Insulin-Like Growth Factor Binding Proteins/metabolism , Insulin-Like Growth Factor I/genetics , Insulin-Like Growth Factor I/metabolism , Insulin-Like Growth Factor II/genetics , Insulin-Like Growth Factor II/metabolism , MicroRNAs/genetics , Neoplasms/genetics , RNA, Long Noncoding/genetics , RNA, Untranslated/genetics , Receptors, Somatomedin/metabolismABSTRACT
Purpose: Testicular cancer (TC) is considered the most commonly diagnosed malignancy in males between 15 and 34 years of age. The objective of this study is to systematically review and meta-analyze studies on fatherhood following treatment for TC. Methods: We reviewed studies reporting on fatherhood following TC from Medline and Embase search engines by developing search strategies. Only studies including patients with TC and at least one reproductive variable were considered as part of the analysis. Estimate of heterogeneity was calculated using the I2 statistic. Meta-analyses employing a fixed effects model were also applied as an additional measure of sensitivity. Results: A total of 27 studies were included which reported on fatherhood after treatment for TC. A meta-analysis of included studies with subgroup analysis was conducted. Subgroup analysis, for the combined studies, indicated an overall pooled pregnancy rate of 22% (95% confidence intervals [CI]: 0.21-0.23; I2 = 98.1%) for couples who conceived after TC. Of those couples that became pregnant, 11% (95% CI: 0.07-0.16; I2 = 8.5%) experienced a miscarriage. Fatherhood was experienced by 37% (95% CI: 0.35-0.39; I2 = 98.1%) of males following treatment for TC. Conclusions: Male cancer patients should be offered discussions, information, and counseling regarding the impact that TC treatment can have on fertility. Furthermore, sperm banking must be recommended to all patients before starting treatment.
Subject(s)
Fertility/physiology , Testicular Neoplasms/complications , Adolescent , Adult , Female , Humans , Male , Young AdultABSTRACT
To better understand the DNA restriction-modification (R-M) systems for more amenable strain development of the alternative industrial ethanologen, Zymomonas mobilis, three gene knockout mutants were constructed. The gene knockout mutants were tested for their DNA restriction activities by the determination of transformation efficiency using methylated and unmethylated foreign plasmid DNAs. Inactivation of a putative mrr gene encoded by ZMO0028 (zmrr) resulted in a 60-fold increase in the transformation efficiency when unmethylated plasmid DNA was used. This indicated that the putative mrr gene may serve as a type IV restriction-modification system in Z. mobilis ZM4. To assign the function of a putative type I DNA methyltransferase encoded by ZMO1933 (putative S subunit) and ZMO1934 (putative M subunit), the putative S subunit was inactivated. The gene inactivation of ZMO1933 resulted in a 30-fold increase in the transformation efficiency when methylated plasmid DNA was introduced, indicating that the putative S subunit possibly serves as a part of functional type I R-M system(s). Growth studies performed on the mutant strains indicate inactivation of the type I S subunit resulted in a lower maximum specific glucose consumption rate and biomass yield, while inactivation of the type IV Zmrr had the opposite effect, with an increase in the maximum specific growth rate and biomass yield.
