The roles of long non-coding RNAs in the necroptotic signaling of colon cancer cells.

BACKGROUND: Necroptosis is a controlled form of necrosis which can be stimulated in cases where the apoptosis signal is absent. Necroptosis can be induced by DR family ligands and by various intracellular and extracellular stimuli that triggers the activation of DR family ligands. Necrostatins, which are specific RIP1 antagonists, prevent necroptosis by inhibiting RIP1 kinase, allowing survival and propagation of cells in the presence of DR ligands. Furthermore, there is a mounting evidence that long non-coding RNA (lncRNA) molecules accomplish vital functions in cell death processes such as apoptosis, autophagy, pyroptosis, and necroptosis. Accordingly, here we aimed to decipher the lncRNAs that are involved in the control and maintenance of necroptosis signaling. METHODS AND RESULTS: Colon cancer cell lines, HT-29 and HCT-116 were used for the study. For the chemical modulation of necroptosis signaling, 5-Fluorouracil, TNF-α and/or Necrostatin-1 were used. Gene expression levels were determined by quantitative real-time PCR. Remarkably, lncRNA P50-associated COX-2 extragenic RNA (PACER) was identified to be suppressed in necroptosis-induced colon cancers, whereas the expression of PACER was restored when necroptosis was suppressed. In addition, no detectable change was observed in HCT-116 colon cancer cells, as these cells lack the expression of RIP3 kinase. CONCLUSIONS: Collectively, current findings clearly imply that PACER have key regulatory roles in the control of necroptotic cell death signaling circuitry. Notably, the tumor promoter activity of PACER might be responsible for the lack of necroptotic death signal in cancer cells. Also, RIP3 kinase seems to be essential component in PACER-associated necroptosis.

Evaluation of cytotoxic, antifungal, and larvicidal activities of different bis-sulfonamide Schiff base compounds.

Schiff bases (imines or azomethines) are versatile ligands synthesized from the condensation of amino compounds with active carbonyl groups and used for many pharmaceutical and medicinal applications. In our study, we aimed to determine the cytotoxic, antifungal and larvicidal activities of biologically potent bis-sulfonamide Schiff base derivatives that were re-synthesized by us. For this aim, 16 compounds were re-synthesized and tested for their cytotoxic, antifungal and larvicidal properties. Among this series, compounds A1B2, A1B4, A4B2, A4B3, and A4B4 were shown to have cytotoxic activity against tested cancer lung cell line (A549). The most potent antifungal activity was observed in compounds A2B1 and A2B2 against all fungi. A1B1 showed the strongest larvicidal effect at all concentrations at the 72nd h (100% mortality). These obtained results demonstrate that these type of bis-substituted compounds might be used as biologically potent pharmacophores against different types of diseases.

Wound healing activity of Salvia huberi ethanolic extract in streptozocin-induced diabetic rats.

Objective: The aim of this study was to examine the in vivo wound healing potential of Salvia huberi Hedge (endemic to Turkey) on excision and incision wound models in diabetic rats. Method: Male Wistar albino rats, 3-4 months old and weighing 180-240g were used. The animals were randomly divided into five groups including Control, Vehicle and Fito reference, and two different concentrations (0.5% and 1% weight/weight (w/w)) of ethanol extract of Salvia huberi were investigated in both wound models on streptozocin-induced diabetic rats using macroscopic, biomechanical, biochemical, histopathological, genotoxic and gene expression methods over both seven and 14 days. Fito cream (Tripharma Drug Industry and Trade Inc., Turkey) was used as the reference drug. Results: A total of 60 rats were used in this study. Salvia huberi ointments at 0.5% and 1% (w/w) concentrations and Fito cream showed 99.3%, 99.4% and 99.1% contraction for excision wounds, and 99.9%, 97.0% and 99% contraction for incision wounds, respectively. In Salvia huberi ointments and Fito cream groups, re-epithelialisation increased dramatically by both day 7 and day 14 (p<0.05). By day 14, low hydroxyproline and malondialdehyde (MDA) levels, and high glutathione (GSH) levels were observed in the Salvia huberi ointment groups. After two application periods, damaged cell percent and genetic damage index values and micronucleus frequency of Salvia huberi ointment treatment groups were lower than Control and Vehicle groups (p<0.001). A growth factor expression reached a high level by day 7 in the Control group; in Salvia huberi-treated groups it was decreased. Conclusion: The study showed that application of Salvia huberi ointments ameliorated the healing process in diabetic rats with excisional and incisional wounds and may serve as a potent healing agent.

Identification of miRNA signatures and their therapeutic potentials in prostate cancer.

BACKGROUND: Herein, we identified miRNA signatures that were able to differentiate malignant prostate cancer from benign prostate hyperplasia and revealed the therapeutic potential of these miRNAs against prostate cancer development. METHODS AND RESULTS: MicroRNA expressions were determined by qPCR. MTT was used for cell viability analysis and immunohistochemistry was performed for Bax/Bcl-2 staining. ELISA was used to measure MMP2/9 levels. Wound healing assay was used for the evaluation of cell migration. Notably, expression levels of miR-125b-5p, miR-145-5p and miR-221-3p were significantly reduced in prostate cancer patients as compared to BPH patients. Moreover, ectopic expression of miR-125b-5p, miR-145-5p and miR-221-3p resulted in significant inhibition of cell proliferation and altered cell morphology. Also, expression level of Bax protein was increased while Bcl-2 level was reduced in cells treated with miR-125b-5p, miR-145-5p and miR-221-3p mimics. Enhanced expression of miR-125b-5p, miR-145-5p and miR-221-3p was also significantly altered the expression of caspase 3 and 8 levels. In addition, MMP9 levels were significantly reduced in cells ectopically expressing miR-221-3p. All miRNA mimics significantly interfered with the migration of prostate cancer cells. CONCLUSIONS: Consequently, our findings point to an important role of these three miRNAs in prostate cancer and indicate that miR-125b-5p, miR-145-5p and miR-221-3p are potential therapeutic targets against prostate cancer.

MTUS1 and its targeting miRNAs in colorectal carcinoma: significant associations.

Deregulated microRNA (miRNA) expression has been shown to be involved in the pathogenesis of several types of cancers including colorectal cancer (CRC). Thus, determining miRNA targets of genes that play critical role in the malignant transformation is very important. Here, expression levels of tumor suppressor microtubule-associated tumor suppressor 1 (MTUS1) and its regulatory miRNAs were reported. Predicted and validated targets of MTUS1 gene was determined by a computational approach. Expressions of MTUS1 and miRNAs were determined by using 96.96 Dynamic Array™ integrated fluidic circuit (Fluidigm). As a result, MTUS1 levels were found to be diminished in formalin-fixed, paraffin-embedded (FFPE) tissue samples of CRC patients compared to controls. Also, several of MTUS1 targeting miRNAs were found to be upregulated in CRC samples (miR-373-3p, 183-5p, 142-5p, 200c-3p, 19a-3p, -20a-5p, -181a-5p, -184, -181d-5p, -372-3p, 27b-3p, 98-5p, -let-7i-5p, -let-7d-5p, -let-7g-5p, -let-7b-5p, and -let-7c-5p). Of these miRNAs, miR-135b-5p, -373-3p, 183-5p, 142-5p, 200c-3p, 19a-3p showed marked expression levels. In contrast, expression levels of let-7a-5p, 7e-5p, 7f-5p, hsa-miR-125a-5p, and 125b-5p were found to be downregulated in CRC tissues. Accordingly, some of the overexpressed miRNAs especially the miR-135b-5p, -373-3p, 183-5p, 142-5p, 200c-3p, and 19a-3p may play key roles in CRC pathophysiology through MTUS1. In contrast, let-7a-5p, 7e-5p, 7f-5p, miR-125a-5p, and 125b-5p may play important roles in CRC carcinogenesis independent from the MTUS1. In conclusion, MTUS1 targeting miRNAs may play key roles in the development of CRC by downregulating tumor suppressor MTUS1.

A novel variable exonic region and differential expression of LINC00663 non-coding RNA in various cancer cell lines and normal human tissue samples.

Long non-coding RNAs (lncRNAs) are found to play crucial roles in several biological processes and have been associated with many complex human diseases including cancers. Several lines of evidences indicate that lncRNAs deregulated in many cancer tissues. In this particular study, differential expression of long intergenic non-coding RNA 663 (LINC00663) was demonstrated in various cancer cell lines and healthy human tissues by using RT-PCR and qPCR methods. While expression level of LINC00663 was most prominent in thyroid gland and uterus, it is least expressed in skeletal muscle tissues. Moreover, LINC00663 was found to be differentially expressed in various cancer cells. Particularly, its expression was highly diminished in DU-145, PC3, HGC-27, CRL-1469, A549, MCF7, and BCPAP cancer cells. Also, LINC00663 expression was most prominent in A172 glioblastoma cells. Additionally, a novel splice variant of LINC00663 RNA was also detected. The sequence and Basic Local Alignment Search Tool (BLAST) analysis results revealed the presence of a novel exonic region between exons 2 and 3. Subsequently, five potential splice variants showing high level of variation have been identified. Secondary structures of these variants with minimum free energy were also demonstrated. Furthermore, putative microRNA (miRNA) binding sites to these variants have been shown. In conclusion, LINC00663 was shown to be differentially expressed in various human tissues and cancer cell lines. Also, LINC00663 undergoes alternative splicing and the novel exonic region alters its secondary structure and its interactions with potential targeting miRNAs. The role of LINC00663 in cancer formation further needs to be investigated with a wide range of studies.

Application of talcum powder, trichloroacetic acid and silver nitrate in female rats for non-surgical sterilization: evaluation of the apoptotic pathway mRNA and miRNA genes.

There are several methods used for non-surgical sterilization in birth control including quinacrine, trichloroacetic acid (TCA), erythromycin, tetracycline, silver nitrate and talcum powder. Among these, talcum powder, TCA and silver nitrate are the most commonly used. However, the toxic and carcinogenic activities of these chemicals in ovarian tissue have been poorly elucidated. This study demonstrates the expression levels of antioxidant, apoptotic and anti-apoptotic genes after administration of talc powder, TCA and silver nitrate for non-surgical sterilization in female rat models. The expression changes of some microRNAs (miR-15b, miR-21, miR-34a and miR-98) that play key roles in the apoptosis pathway were also included. All expression analyses were evaluated with real-time PCR. The expression levels of all genes appeared to be upregulated in the talcum powder group, but the results were not statistically significant. Increased expression of Gsr and Sod1 genes was statistically significant in the talcum powder group. In TCA and silver nitrate group, expression of all genes was appeared to be elevated but only the Gsr expression was statistically significant in the TCA-administrated group; there were no statistically significant changes in the silver nitrate group. miRNA expression levels were increased in talcum powder and TCA-administrated groups, but these results were not significant. Expression levels of miR-15b, miR-21 and miR-98 in the silver nitrate group were significantly increased. Consequently, these chemicals appear to be non-carcinogenic agents for rat ovarian tissue which do not induce apoptosis. However, talcum powder and TCA can be considered as agents that are toxic to ovarian tissue.

Insecticide imidacloprid influences cognitive functions and alters learning performance and related gene expression in a rat model.

The potential toxic effects of several pesticides, including imidacloprid on non-target organisms have not been clearly established. Also, the chronic effects of non-toxic doses on cognitive function in mammals are unknown. In this study, the effects of different doses of imidacloprid on learning and memory of infant and adult rats were evaluated, and the expressions of genes synthesizing proteins known to be associated with learning in brain tissues were also documented. 0.5, 2 and 8 mg/kg doses of imidacloprid were administered to newborn infant and adult Wistar albino rats by gavage. Their learning activities were evaluated, and the expression levels of the inotropic glutamate receptor GRIN1, synoptophysin, growth-associated protein 43 and the muscarinic receptor M1 in hippocampus were determined by real-time PCR method. Learning activities were diminished significantly at 2 and 8 mg/kg doses in the infant model groups and at 8 mg/kg dose in adult rats. Also, expression levels of GRIN1, SYP and GAP-43 were found to be insignificantly altered. Only the expression of M1 were significantly changed in high doses of adult group. Thus imidacloprid in high doses causes deterioration in cognitive functions particularly in infant rats, and this deterioration may be associated with changes in the expressions of related genes.

Differential expression of the UGT1A family of genes in stomach cancer tissues.

Uridine 5'-diphospho-glucuronosyltransferases (UGT) are the key players in the biotransformation of drugs, xenobiotics, and endogenous compounds. Particularly, UDP-glucuronosyltransferase 1A (UGT1A) participates in a wide range of biological and pharmacological processes and plays a critical role in the conjugation of endogenous and exogenous components. Thirteen alternative splicing products were produced from UGT1A gene locus designated as UGT1A1 and UGT1A3-10. A growing amount of evidence suggests that they have important roles in the carcinogenesis which is well documented by colon, liver, pancreas, and kidney cancer studies. Here, we report differential expressions of UGT1A genes in normal and tumor tissues of stomach cancer patients. Total numbers of 49 patients were enrolled for this study, and expression analysis of UGT1A genes was evaluated by the real-time PCR method. Accordingly, UGT1A1, UGT1A8, and UGT1A10 were found to be upregulated, and UGT1A3, UGT1A5, UGT1A7, and UGT1A9 were downregulated in stomach tumors. No expression changes were observed in UGT1A4. Also, UGT1A6 transcription variants were significantly upregulated in stomach cancer tissues compared to normal stomach tissue. Additionally, UGT1A7 gene showed highest expression in both normal and tumoral tissues, and interestingly, UGT1A7 gene expression was significantly reduced in stage II patients as compared to other patients. In conclusion, UGT1A genes are differentially expressed in normal and tumoral stomach tissues and expression changes of these genes may affect the development and progression of various types of cancer including the cancer of the stomach.

The role of the UTS2 gene polymorphisms and plasma Urotensin-II levels in breast cancer.

Breast cancer is the most common malignancy predominantly affecting women. To date, numerous numbers of studies were reported novel genetic contributors with diagnostic, prognostic, and therapeutic potential for the breast carcinogenesis. However, the role of urotensin-II in breast carcinogenesis has not been elucidated yet. Urotensin-II is a somatostatin-like cyclic tiny peptide identified by its potent vasoconstrictor activity. Soon after its discovery, its involvement in many disease states as well as its expression in various tissues including the tumors have been demonstrated. Moreover, there is strong evidence that suggest urotensin-II as the significant contributor of angiogenesis as well as cell proliferation and tumor biology. In this study, enzyme-linked immunosorbent assay (ELISA) and restriction fragment length polymorphism analysis were used to evaluate plasma levels of urotensin-II and Thr21Met and Ser89Asn polymorphisms of UTS2 gene in breast cancer patients. In the present case-control study, we noticed a significant decrease in the levels of urotensin-II protein in the plasma of the breast cancer patients (p < 0.05). Also, Thr21Met polymorphism in the UTS2 gene was associated with the risk of developing breast cancer (p < 0.0001), whereas the genotype frequency of Ser89Asn was found to be similar in patients and controls (p > 0.05). In addition, we demonstrated the gradual decreasing of urotensin-II protein levels from TT and TM to MM genotypes. In conclusion, these results strongly suggest that urotensin-II could contribute to breast carcinogenesis and Thr21Met polymorphism can be an important risk factor in developing breast tumors.

Expression patterns of miR-221 and its target Caspase-3 in different cancer cell lines.

Caspases are important initiators and most well-known finishers of apoptosis. By changing the death propagation homeostatic equilibrium, their different expression patterns might trigger the progression of hazardous diseases like cancer. miR-221 is an oncogenic miRNA. It is known to have both anti-angiogenic and angiogenic effect. The aim of this work was to compare the expression levels of miR-221 and its target caspase-3 in different cancer cell lines and to find out a relationship between these two. We also tried to establish a prominent relationship between miR-221 and its role in apoptosis by studying their expression levels. Our results indicate that expression of caspase-3 is quite lower as compared to miR-221 expression in all of the selected cancer cell lines. As a result, we conclude that miR-221 may have a crucial role in repressing the expression of caspase-3 which may contribute to a lower apoptotic rate, thus supporting the selection of more aggressive cancer cells. To our knowledge, this is the first study related to the expression levels of caspase-3 and miR-221 in different cell lines at the same time. We expect that our study might pave the way for better understanding the role of miR-221 in apoptotic regulation of caspase-3.

Expressions of TRPM6 and TRPM7 and histopathological evaluation of tissues in ischemia reperfusion performed rats.

There is very little work on the expression of TRPM6/7 in ischemia reperfusion models. In previous studies, after ischemia, reperfusion had been kept limited to 24 h, yet in our study, expressions of these channels were elucidated after its modification to 48 h to establish what kind of changes renal tissues undergo. For the current study, 20 Wistar albino rats were divided into two groups equally. Group I: control group, Group II = I/R group (60 min ischemia + 48 h reperfusion). For the mRNA analysis, right kidneys of I/R group was used as a reference in order to eliminate genetic differences. The left renal artery (I/R generated part) of I/R area was removed from all rats in the second group. Likewise, normal tissues of right renal artery were removed from all rats. Histopathologic scoring of the tissue samples were achieved semi-quantitatively according to normal tissue composition. Consequently, both TRPM6 and TRPM7 expression levels were decreased in all groups according to control groups, yet results were not counted as significant (p > 0.05). Additionally, correlation analysis confirmed these results. Also, I/R performed kidneys had more tissue damage compared to control group. To conclude, our study results suggest that TRPM6/7 expressions may be increased and after 48 h of reperfusion expression levels of these two stored to normal levels. At the same time, damages have occurred in renal tissues after ischemia. These damages were considered to be resulted from the oxidative effects as previously reported.

The fate and function of non-coding RNAs during necroptosis.

Necroptosis is a novel form of cell death which is activated when apoptotic cell death signals are disrupted. Accumulating body of observations suggests that noncoding RNAs, which are the lately discovered mystery of the human genome, are significantly associated with necroptotic signaling circuitry. The fate and function of miRNAs have been well documented in human disease, especially cancer. Recently, lncRNAs have gained much attention due to their diverse regulatory functions. Although available studies are currently based on bioinformatic analysis, predicted interactions desires further attention, as these hold significant promise and should not be overlooked. In the light of these, here we comprehensively review and discuss noncoding RNA molecules that play significant roles during execution of necroptotic cell death.

Necroptosis is a novel form of cell death triggered by disrupted apoptotic signals. noncoding RNAs, a mystery of the human genome, are significantly associated with necroptotic signaling. Their diverse regulatory functions, particularly in cancer, warrant further attention due to their potential.

Identification of non-coding RNA signatures in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a deadly, chronic, progressive, irreversible interstitial lung disease characterized by the formation of scar tissue resulting in permanent lung damage. The average survival time following diagnosis is only 3-5 years, with a 5-year survival rate shorter than that of many cancers. Alveolar epithelial cell injury followed by irregular repair is the primary pathological process observed in patients with IPF. An evident characteristic of IPF is the development of fibroblastic foci representing active fibrotic areas. Most of the cells within these foci are believed to be myofibroblasts, which are thought to be the primary source of abnormal extracellular matrix production in IPF. The lung phenotype in IPF is characterized by significantly different processes from healthy lungs, including irregular apoptosis, oxidative stress, and epithelial-mesenchymal transition (EMT) pathways. AIMS: The exact cause of IPF is not fully understood and remains mysterious. It is not suppressing that non-coding RNAs are involved in the development and progression of IPF. Accordingly, here we aimed to identify non-coding RNA molecules during TGFß-induced myofibroblast activation. METHODS: Differential expression and functional enrichment analysis were employed to reveal the impact of non-coding RNAs during TGFß-associated lung fibrosis. RESULTS: Remarkably, LOC101448202, CZ1P-ASNS, LINC01503, IER3-AS1, MIR503HG, CLMAT3, LINC02593, ACTA2-AS1, LOC102723692, LOC107985728, and LOC105371064 were identified to be differentially altered during TGFß-stimulated myofibroblast activation. CONCLUSIONS: These findings strongly suggest that the mechanism of lung fibrosis is heavily under control of non-coding RNAs, and RNA-based therapies could be a promising approach for future therapeutic interventions to lung fibrosis.

Long non-coding RNA signatures in non-small cell lung cancer and their clinicopathological significance.

Lung cancer is the most common type of cancer in our country and worldwide, and it is a leading cause of cancer-related deaths. According to the latest global cancer statistics, lung cancer was identified as the second most common type of cancer, and the leading cause of cancer-related deaths. Long non-coding RNAs (lncRNAs) are a highly heterogeneous class of RNA molecules sharing many characteristics with mRNAs, except for the protein-coding potential. Accumulating mass of evidence suggest that lncRNAs play key regulatory roles during the multistep formation of human cancers including lung cancer. In previous studies, it has been shown that many lncRNA molecules play significant roles in the formation and progression of lung cancer. However, there are still numerous lncRNA molecules in lung cancer whose roles remain unknown. Accordingly, here we sought to ascertain the diagnostic and prognostic value of lncRNAs by analyzing the expression profiles of THRIL, NEAT1, and LOC105376095 in lung cancer. Remarkably, NEAT1 and LOC105376095 but not THRIL were identified to be differentially expressed in tissues of lung tumors. More importantly, LOC105376095, a yet uncharacterized lncRNA molecule, was significantly associated with the disease severity. Collectively, NEAT1 and LOC105376095 hold promise as potential diagnostic and prognostic biomarkers for lung cancer, presenting opportunities for targeted therapeutic interventions in the future.

Association transient receptor potential melastatin channel gene polymorphism with primary open angle glaucoma.

PURPOSE: Genetic factors are shown to have a role in the development of primary open angle glaucoma (POAG). The aim of this study was to determine the effects of genetic polymorphisms of transient receptor potential melastatin (TRPM) channel genes on the risk of POAG in a Turkish population. METHODS: Genomic DNA was extracted from the leukocytes of the peripheral blood, and 26 single nucleotide polymorphisms in the TRPM channel genes were analyzed in 179 patients with POAG and in 182 healthy controls of similar age by using the BioMark HD dynamic array system. RESULTS: There were marked changes in the genotype (TT, 26.8%; CT, 66.7%; CC, 6.5%) and allele (T, 60.1%; C, 39.9%) frequencies for the TRPM5 gene rs34551253 (Ala456Thr, in exon 9) polymorphism in patients when compared to the controls (TT, 11.3%; CT, 74.6%; CC, 14.1%, p = 0.0009; T, 48.6%; A, 51.4%, p = 0.0063). However, no associations with the other 25 polymorphisms studied were found. CONCLUSIONS: This is the first study to examine the involvement of TRPM channel gene variations in the risk of incident POAG. This study demonstrated that the TRPM5 gene rs34551253 (Ala456Thr) polymorphism may be associated with increased risk of developing POAG in the Turkish population.

Unveiling the therapeutic potential of natural-based anticancer compounds inducing non-canonical cell death mechanisms.

In the Mid-19th century, Rudolf Virchow considered necrosis to be a prominent form of cell death; since then, pathologists have recognized necrosis as both a cause and a consequence of disease. About a century later, the mechanism of apoptosis, another form of cell death, was discovered, and we now know that this process is regulated by several molecular mechanisms that "programme" the cell to die. However, discoveries on cell death mechanisms are not limited to these, and recent studies have allowed the identification of novel cell death pathways that can be molecularly distinguished from necrotic and apoptotic cell death mechanisms. Moreover, the main goal of current cancer therapy is to discover and develop drugs that target apoptosis. However, resistance to chemotherapeutic agents targeting apoptosis is mainly responsible for the failure of clinical therapy and adverse side effects of the chemotherapeutic agents currently in use pose a major threat to the well-being and lives of patients. Therefore, the development of natural-based anticancer drugs with low cellular and organismal side effects is of great interest. In this comprehensive review, we thoroughly examine and discuss natural anticancer compounds that specifically target non-canonical cell death mechanisms.

Non-coding RNA variations in oral cancers: A comprehensive review.

For a long time, scientists believed that only changes or mutations in protein-coding genes were responsible for the onset and development of cancer. However, the discovery of non-coding RNAs has revolutionized our understanding of tumor biology. Now, we are aware that non-coding RNA molecules have a higher influence on cancer biology than previously thought. The discovery of non-coding RNAs also presented several challenges because they are relatively unstable under laboratory conditions and can lead to false-positive and false-negative results in expression analysis. Therefore, variation analysis may provide more accurate results for understanding the role and impact of these molecules in cancer biology. Accordingly, in the present comprehensive review, we aimed to review and discuss current knowledge on non-coding RNA alterations linked to the development and progression of oral malignancies. Collectively, variations of non-coding RNA molecules seem to have great impact in the development and progression of oral cancers.

The Role and Antagonistic Effects of miR-16-5p in the Regulation of ADP-Ribosylation Factor-Like Tumor Suppressor Gene 1 in Lung Cancer Cells.

OBJECTIVE: ADP-ribosylation factor-like tumor suppressor gene 1 is a member of the Ras superfamily of small guanosine triphosphatases that are known to be involved in multiple regulatory pathways in the multistage development of human cancers. Also, ADP-ribosylation factor-like tumor suppressor gene 1 expression levels have been reported to be dramatically lower in both cancer cell lines and tumor tissues compared to controls. Accordingly, defects in the regulation of the ADP-ribosylation factor-like tumor suppressor gene 1 gene seems have key tumor suppressive effects in the formation and development of human cancers including lung cancer. Moreover, microRNAs regulating the expression of ADP-ribosylation factor-like tumor suppressor gene 1 have not been described previously. Accordingly, the present study aimed to reveal the influence of miR-16-5p on the regulation of ADP-ribosylation factor-like tumor suppressor gene 1 gene. MATERIALS AND METHODS: A549 lung adenocarcinoma cells were used. For the overexpression and silencing experiments of miR-16-5p synthetic microRNA mimics and inhibitors were used, respectively. Gene expression analyses were achieved with the help of quantitative real-time polymerase chain reaction. RESULTS: MiR-16-5p was identified to be predictive target of ADP-ribosylation factor-like tumor suppressor gene 1 and directly targets the expression of ADP-ribosylation factor-like tumor suppressor gene 1 as revealed by the overexpression and silencing experiments. Specifically, it was found that miR-16-5p-overexpressed A549 cells showed a decrease in ADP-ribosylation factor-like tumor suppressor gene 1 gene expression, whereas miR16-5p-suppressed cells showed an increase in expression. These findings possibly suggest that miR-16-5p is the direct regulatory microRNA that posttranscriptionally regulates the expression of ADP-ribosylation factor-like tumor suppressor gene 1. CONCLUSION: Collectively, miR-16-5p seems to be a key regulatory molecule involved in the posttranscriptional regulation of the ADP-ribosylation factor-like tumor suppressor gene 1, and it might be responsible for the downregulation of this gene in lung cancer.

MicroRNAs and cardiac fibrosis: A comprehensive update on mechanisms and consequences.

Fibrosis is a pathological wound-healing mechanism that results by the overactivation of fibroblasts. Fibrosis can become obstructive and deleterious during regeneration of various body tissues including cardiac muscle. This ultimately results in the development of cardiac fibrosis, characterized by an excessive buildup of extracellular matrix proteins. Thus, it could lead to arrhythmias and heart failure which creates a leading public health burden worldwide. MiRNAs are small non-coding RNAs with great potential for diagnostic and therapeutic purposes. Mounting evidence indicates that miRNAs are involved in the deregulation of tissue homeostasis during myocardial fibrosis. For instance, miRNAs that are implicated in the regulation of TGF-beta signaling pathway have been reported to be significantly altered in myocardial fibrosis. Accordingly, in this comprehensive review, we discuss and highlight recent available data on the role of miRNAs during myocardial fibrosis, providing valuable insights into the miRNA modulation of cardiac fibrosis and miRNAs targets that can be used in the future therapeutic interventions to cardiac fibrosis.