miRNA-mediated regulation of clock gene expression in men and women with colorectal cancer and possible consequences for disease management.

Background: The incidence and mortality of colorectal cancer (CRC) are persistently higher in men than in women. CRC malignancy is strongly influenced by small non-coding RNAs (miRNAs). Moreover, deregulation of the circadian molecular oscillator has been associated with CRC facilitation.

Impact of Long-Lasting Environmental Factors on Regulation Mediated by the miR-34 Family.

The present review focuses on the interactions of newly emerging environmental factors with miRNA-mediated regulation. In particular, we draw attention to the effects of phthalates, electromagnetic fields (EMFs) and a disrupted light/dark cycle. miRNAs are small non-coding RNA molecules with a tremendous regulatory impact, which is usually executed via gene expression inhibition.

Effect of miR-34a on the expression of clock and clock-controlled genes in DLD1 and Lovo human cancer cells with different backgrounds with respect to p53 functionality and 17β-estradiol-mediated regulation.

The small non-coding RNA miR-34a is a p53-regulated miRNA that acts as a tumour suppressor of colorectal cancer (CRC). Oncogenesis is also negatively influenced by deregulation of the circadian system in many types of tumours with various genetic backgrounds. As the clock gene per2 was recently recognized as one of the target genes of miR-34a, we focused on the miR-34a-mediated influence on the circadian oscillator in CRC cell lines DLD1 and LoVo, which differ in their p53 status.

2.4 GHz Electromagnetic Field Influences the Response of the Circadian Oscillator in the Colorectal Cancer Cell Line DLD1 to miR-34a-Mediated Regulation.

Radiofrequency electromagnetic fields (RF-EMF) exert pleiotropic effects on biological processes including circadian rhythms. miR-34a is a small non-coding RNA whose expression is modulated by RF-EMF and has the capacity to regulate clock gene expression. However, interference between RF-EMF and miR-34a-mediated regulation of the circadian oscillator has not yet been elucidated.

The 24-h pattern of dgcr8, drosha, and dicer expression in the rat suprachiasmatic nuclei and peripheral tissues and its modulation by angiotensin II.

Study was focused on regulatory interactions between the circadian system and the renin-angiotensin system in control of microRNA (miRNA) biosynthesis. Responsiveness of the miRNA biosynthetic pathway, selected pre-miRNAs and clock genes to angiotensin II (AngII) infusion was analysed in the suprachiasmatic nuclei (SCN), liver, kidney and heart during a 24-h cycle. per2 exerted a rhythmic expression profile in all analysed tissues.

Effect of 17β-estradiol on the daily pattern of ACE2, ADAM17, TMPRSS2 and estradiol receptor transcription in the lungs and colon of male rats.

Covid-19 progression shows sex-dependent features. It is hypothesized that a better Covid-19 survival rate in females can be attributed to the presence of higher 17β-estradiol (E2) levels in women than in men. Virus SARS-CoV-2 is enabled to enter the cell with the use of angiotensin converting enzyme 2 (ACE2).

Food reward induction of rhythmic clock gene expression in the prefrontal cortex of rats is accompanied by changes in miR-34a-5p expression.

The current study is focused on mechanisms by which the peripheral circadian oscillator in the prefrontal cortex (PFC) participates in food reward-induced activity. The experimental group of male Wistar rats was trained to receive a food reward with a low hedonic and caloric value. Afterwards, animals were exposed to a 5 h phase advance.

miRNA Clusters with Up-Regulated Expression in Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common malignancies in Europe and North America. Early diagnosis is a key feature of efficient CRC treatment. As miRNAs can be used as CRC biomarkers, the aim of the present study was to analyse experimentally validated data on frequently up-regulated miRNA clusters in CRC tissue and investigate their members with respect to clinicopathological characteristics of patients.

miRNA Clusters with Down-Regulated Expression in Human Colorectal Cancer and Their Regulation.

Regulation of microRNA (miRNA) expression has been extensively studied with respect to colorectal cancer (CRC), since CRC is one of the leading causes of cancer mortality worldwide. Transcriptional control of miRNAs creating clusters can be, to some extent, estimated from cluster position on a chromosome. Levels of miRNAs are also controlled by miRNAs "sponging" by long non-coding RNAs (ncRNAs).

Expression of miR-34a-5p is up-regulated in human colorectal cancer and correlates with survival and clock gene PER2 expression.

Colorectal cancer represents a leading cause of cancer death. MicroRNAs (miRNAs) are small non-coding RNA molecules that have been extensively studied in tumours, since changes in their levels can reveal patient prognosis. Cancer progression is also influenced by the circadian system whose functioning is based on the rhythmic expression of clock genes.

Sex and salt intake dependent renin-angiotensin plasticity in the liver of the rat.

Objective: Epidemiological studies confirm that hypertensive patients respond differently to renin-angiotensin system (RAS) inhibition depending on their gender. The aim of present work is to focus on sex-dependent differences in RAS regulation under conditions of increased salt intake.

Method: To investigate RAS, we measured the expression of angiotensinogen (Agt) mRNA, angiotensin receptor type 1 (AT1) mRNA and mitochondria assembly receptor (MasR) in the liver of rats under control conditions and after feeding with a salt diet (2% NaCl).

Sex-dependent correlation between survival and expression of genes related to the circadian oscillator in patients with colorectal cancer.

Recent evidence supports the important role of the circadian system in cancer progression in humans. The aim of the present study is to evaluate clock (cry1, cry2 and per2) and clock-controlled (vascular endothelial growth factor-a, early growth response protein 1 and estrogen receptor β) gene expression in colorectal cancer and adjacent tissue and identify a possible link between survival of patients and expression of above mentioned genes. The study includes 64 patients of both sexes with previously diagnosed colorectal cancer.

Angiotensin II in the Human Physiology: Novel Ways for Synthetic Compounds Utilization.

Background: Renin-angiotensin system (RAS) and its main product Angiotensin II (AngII) are in the focus of the pharmacological industry mainly because of hypertension treatment. Up-regulated RAS is generally associated with cardiovascular diseases and consequent organs injuries. The classic inhibition of RAS is based on the blocking of the type 1 AngII receptors and inhibition of ACE.

Endocrine and cardiovascular rhythms differentially adapt to chronic phase-delay shifts in rats.

Disturbances in regular circadian oscillations can have negative effects on cardiovascular function, but epidemiological data are inconclusive and new data from animal experiments elucidating critical biological mechanisms are needed. To evaluate the consequences of chronic phase shifts of the light/dark (LD) cycle on hormonal and cardiovascular rhythms, two experiments were performed. In Experiment 1, male rats were exposed to either a regular 12:12 LD cycle (CONT) or rotating 8-h phase-delay shifts of LD every second day (SHIFT) for 10 weeks.

Expression of cell cycle regulatory factors hus1, gadd45a, rb1, cdkn2a and mre11a correlates with expression of clock gene per2 in human colorectal carcinoma tissue.

Deregulated expression of clock gene per2 has previously been associated with progression of cancer. The aim of the present study was to identify genes related to per2 expression and involved in cell cycle control. Patients surgically treated for colorectal carcinoma with up-regulated and down-regulated per2 expression in cancer versus adjacent tissue were studied.

Effect of angiotensin II on rhythmic per2 expression in the suprachiasmatic nucleus and heart and daily rhythm of activity in Wistar rats.

Endogenous daily rhythms are generated by the hierarchically organized circadian system predominantly synchronized by the external light (L): dark (D) cycle. During recent years several humoral signals have been found to influence the generation and manifestation of daily rhythm. Since most studies have been performed under in vitro conditions, the mechanisms employed under in vivo conditions need to be investigated.

Melatonin and clock genes expression in the cardiovascular system.

Generation of circadian oscillations is based on rhythmic expression of clock genes and subsequent post-transcriptional and post-translational modifications. In addition to the central circadian oscillator - the suprachiasmatic nucleus (SCN), peripheral oscillators have been demonstrated in many tissues, including the heart and blood vessels. Melatonin mediates cyclic lighting conditions to rhythmic endocrine signal and is able to synchronize neuronal firing in the SCN via membrane receptors.

Circadian melatonin production develops faster in birds than in mammals.

The development of circadian rhythmicity of melatonin biosynthesis in the pineal gland starts during embryonic period in birds while it is delayed to the postnatal life in mammals. Daily rhythms of melatonin in isolated pinealocytes and in intact pineal glands under in vivo conditions were demonstrated during the last third of embryonic development in chick embryos, with higher levels during the dark (D) than during the light (L) phase. In addition to the LD cycle, rhythmic temperature changes with the amplitude of 4.

Effect of phase delay lighting rotation schedule on daily expression of per2, bmal1, rev-erbα, pparα, and pdk4 genes in the heart and liver of Wistar rats.

Under synchronized conditions daily rhythms run in precise phase relationships. Long lasting shift-work disturbs circadian rhythms and causes metabolism dysfunction. As a result of frequent shifts of the light (L):dark (D) cycle the circadian system has to adjust to a new regimen repeatedly, and organism can never achieve complete adjustment of all circadian rhythms.

Effect of rhythmic melatonin administration on clock gene expression in the suprachiasmatic nucleus and the heart of hypertensive TGR(mRen2)27 rats.

Objectives: Plasma melatonin concentrations in non-dipping patients show a blunted daily rhythm. Melatonin has a capacity to improve disturbances in biological rhythms. Hypertensive TGR(mRen2)27 (TGR) rats with an upregulated renin-angiotensin system and inverted blood pressure profile were used to elucidate whether melatonin is able to influence the control of blood pressure.

Ontogeny of circadian oscillations in the heart and liver in chicken.

The circadian system drives postnatally rhythmic processes in the peripheral tissues. To extend information about embryonic stages, ontogeny of the circadian oscillations in chicken (Gallus gallus) heart and liver was analyzed. Nineteen day old embryos and 4-day old chicks were synchronized to a light:dark cycle and then the effects of light pulses applied during the dark and subjective light phases of the 24 h cycle were tested.

Effect of L-NAME-induced hypertension on melatonin receptors and melatonin levels in the pineal gland and the peripheral organs of rats.

Melatonin plays a role in blood pressure (BP) control. The aim of this study was to determine whether melatonin concentrations and melatonin receptor levels are altered in L-NAME-treated, NO-deficient hypertensive rats. Two groups of male adult Wistar rats were investigated: rats (n=36) treated with NO-synthase inhibitor L-NAME (40 mg kg(-1)) and age-matched controls (n=36).

Endocrine rhythms and expression of selected genes in the brain, stellate ganglia, and adrenals of hypertensive TGR rats.

Hypertensive TGR(mRen2)27 (TGR) rats represent a strain with genetically upregulated renin-angiotensin-aldosterone system. Simultaneously with development of hypertension, a daily profile in blood pressure (BP) inverts and in mature TGR rats BP is higher during the lighttime (L) than the darktime (D). Physiological mechanisms of inverted BP rhythm generation are not understood.