MicroRNAs (miRNAs) are noncoding small nucleic acids that contain ~22 nucleotides and are considered to promote the degradation or inhibit the translation of mRNA by targeting its 3\'‑untranslated region. However, growing evidence has revealed that nuclear miRNAs, combined with gene promoters or enhancers, are able to directly mediate gene transcription. These miRNAs exert a critical influence on cancer progression by affecting cell growth, migration and invasion. In this review, the direct regulation of gene expression by nuclear miRNAs at the transcriptional level was discussed and summarized, and their mechanisms of action in cancers were highlighted with reference to the various body systems.

Bacillus subtilis is a Gram-positive bacterium that has gained an unprecedented reputation as an expression system at the industrial scale due to characteristics such as GRAS (Generally recognized as safe), ease of genetic manipulation, high growth rate on the cheap substrate, and short fermentation cycle. This expression system has been widely accepted for the production of various chemicals, pharmaceutical products, food products, proteins, and enzymes. But there are various hurdles to optimized production of heterologous protein in this expression system due to a lack of understanding regarding metabolic pathways and expression elements. In this review, we have emphasized strategies that can enhance the expression level of heterologous proteins in B. subtilis. These strategies included optimization of B. Subtilis strain, expression elements such as promotors, UTR (Untranslated region), RBS (Ribosome binding site), signal peptide, and metabolic pathways. Finally, contemporary challenges and future perspectives of B. subtilis as an industrial scale expression system were discussed.

MicroRNAs (miRNAs/miRs) are a type of endogenous non‑coding small RNA that regulates gene expression. miRNAs regulate gene expression at the post‑transcriptional level by targeting the 3\'‑untranslated region (3\'UTR) of cytoplasmic messenger RNAs (mRNAs). Recent research has confirmed the presence of mature miRNAs in the nucleus, which bind nascent RNA transcripts, gene promoter or enhancer regions, and regulate gene expression via epigenetic pathways. Some miRNAs have been shown to function as oncogenes or tumor suppressor genes by modulating molecular pathways involved in human cancers. Notably, a novel molecular mechanism underlying the dysregulation of miRNA expression in cancer has recently been discovered, indicating that miRNAs may be involved in tumorigenesis via a nuclear function that influences gene transcription and epigenetic states, elucidating their potential therapeutic implications. The present review article discusses the import of nuclear miRNAs, nucleus‑cytoplasm transport mechanisms and the nuclear functions of miRNAs in cancer. In addition, some software tools for predicting miRNA binding sites are also discussed. Nuclear miRNAs supplement miRNA regulatory networks in cancer as a non‑canonical aspect of miRNA action. Further research into this aspect may be critical for understanding the role of nuclear miRNAs in the development of human cancers.

Cyclins are key regulators of cell cycle progression and survival. Particularly cyclins D (cyclin D1, D2, and D3) act in response to the mitogenic stimulation and are pivotal mediators between proliferative pathways and the nuclear cell cycle machinery. Dysregulation of cyclins expression results in impaired development, abnormal cell growth or tumorigenesis. In this review we summarize current knowledge about regulatory role of the cyclin D promoters, transcriptional factors: regulators, co-activators and adaptor proteins necessary to their activation. We focused on the intracellular signaling pathways vital to cell growth, differentiation and apoptosis including transcription factor families: activator protein 1 (AP1), nuclear factor (NFκB), signal transducer and activator of transcription (STAT), cAMP response element-binding protein (CREB) and Sp/NF-Y, with a special insight into the tissue specific cyclin representation.

Steroid hormones modulate several important biological processes like metabolism, stress response, and reproduction. Steroidogenesis drives reproductive function wherein development and differentiation of undifferentiated gonads into testis or ovary, and their growth and maturation, are regulated. Steroidogenesis occurs in gonadal and non-gonadal tissues like head kidney, liver, intestine, and adipose tissue in teleosts. This process is regulated differently through multi-level modulation of promoter motif transcription factor regulation of steroidogenic enzyme genes to ultimately control enzyme activity and turnover. In view of this, understanding teleostean steroidogenesis provides major inputs for technological innovation of pisciculture. Unlike higher vertebrates, steroidal intermediates and shift in steroidogenesis is critical for gamete maturation in teleosts, more essentially oogenesis. Considering these characteristics, this review highlights the promoter regulation of steroidogenic enzyme genes by several transcription factors that are involved in teleostean steroidogenesis. It also addresses different methodologies involved in promoter regulation studies together with glucocorticoids and androgen relationship with reference to teleosts.

BACKGROUND: Mutations in the telomerase reverse transcriptase promoter (TERTp) region have been associated with worse prognosis in some cancers. Meningiomas are the most common type of primary central nervous tumors, and evaluation of the prognostic significance of TERTp mutations across the literature is lacking. The aim of this study was to pool all current evidence to assess for clinical relevance of TERTp mutations in meningioma and survival effect.
METHODS: Searches of seven electronic databases from inception to September 2018 were conducted following the appropriate guidelines. Two hundred and twenty seven articles were identified for screening. Hazard ratio (HR) and mean difference (MD) statistics were obtained and pooled utilizing both fixed- and random-effect (RE) models. Meta-regression was utilized to determine potential sources of heterogeneity and statistical influence.
RESULTS: A total of five retrospective observational cohort studies describing 532 meningioma patients satisfied selection criteria. The incidence of TERTp mutations was 8%, and was associated with significantly worse prognosis (HR 3.79; P = 0.005) and significantly shorter overall survival (MD 59.8 months; P = 0.037) by RE modelling. Meningioma grade was not significantly associated with a TERTp mutation effect, however, preliminary meta-regression trends indicated this may be significant once greater statistical power is achieved.
CONCLUSIONS: The current evidence indicates the presence of a TERTp mutation in meningioma can be associated with worse prognosis, and shorter overall survival. Routine detection in greater numbers will allow for further validation, as well as delineate the effect across histological grades. By identifying this subgroup of meningioma patients early in management, it may support more frequent follow-up and aggressive management to optimize survival outcomes.

OBJECTIVE: Epigenetic inactivation of tumor suppressor genes is an important molecular mechanism in the formation and development of human tumors. The purpose of our study was to evaluate the correlation between the methylation level of the secreted frizzled-related protein 1 (SFRP1) gene and the risk of renal cell carcinoma (RCC).
METHODS: The relevant literature was searched in detail in several electronic databases. The methodological heterogeneity was analyzed by meta-regression and subgroup analyses. The odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated to summarize the dichotomous outcomes of our meta-analysis.
RESULTS: The ten included articles contained 535 RCC samples and 475 normal controls. The results demonstrated that the methylation level of the SFRP1 promoter region was significantly correlated with an increased incidence of RCC (OR=13.72; 95% CI: 6.01-31.28; P=0.000). Furthermore, the eligible studies that had sufficient clinical data about the RCC cases were included in the analysis, and the results indicated that the frequency of SFRP1 promoter methylation was associated with a higher histological grade (P=0.000), tumor stage (P=0.033), tumor size (≥5 cm; P=0.029), and distant metastasis (P=0.047).
CONCLUSIONS: Our results indicate that the methylation level of the SFRP1 promoter region is increased in patients with RCC compared to normal controls and might be involved in the occurrence and development of RCC. Additional well-designed studies are needed to further verify our conclusions.

In past decades, prediction of genes in DNA sequences has attracted the attention of many researchers but due to its complex structure it is extremely intricate to correctly locate its position. A large number of regulatory regions are present in DNA that helps in transcription of a gene. Promoter is one such region and to find its location is a challenging problem. Various computational methods for promoter prediction have been developed over the past few years. This paper reviews these promoter prediction methods. Several difficulties and pitfalls encountered by these methods are also detailed, along with future research directions.

BACKGROUND: The variation in clinical outcome of hepatitis B virus (HBV) infection is determined by virological, immunological and host genetic factors. Genes encoding cytokines are one of the candidates among host genetic factors. Polymorphisms in gene promoter can lead to different levels of cytokine expression and unique immune response. Being involved in the inflammatory cytokine network, interleukin-18 (IL-18) plays an important role in pathogenesis of HBV infection. The aim of this review is considering available literature on the association between IL-18 gene promoter single nucleotide polymorphisms (-137 C/G and -607 A/C) and susceptibility to chronic HBV infection.
METHODS: Published literature from PubMed, EMBASE, and other databases were retrieved. All studies investigating the association of IL-18 gene promoter SNPs, -137 C/G and -607 A/C, with susceptibility to chronic HBV infection were included.
RESULTS: Findings showed that the genotype -607A/A is associated with the susceptibility to chronic hepatitis B. Furthermore, allele C at position -137 is suggested to play a protective role against development of chronic HBV infection.
CONCLUSIONS: Host genetic factors play an important role in determining the outcome of HBV infection. It is suggested that IL-18 genotype -607 A/A is associated with susceptibility to chronic hepatitis B. Furthermore, the carriage of allele C at position -137 may play a protective role in the development of chronic HBV infection.