Expression analysis of cytoskeleton regulator RNA and Cyclin Dependent Kinase Inhibitor 2B genes in breast cancer.

BACKGROUND: Breast cancer has been found to be associated with deregulation of several non-coding genes and mRNA coding genes. OBJECTIVE: To assess expressions of CYTOR and CDKN2B in breast cancer and adjacent samples and find their relevance with clinical data. METHODS: We enumerated expression level of CDKN2B and CYTOR in 43 newly diagnosed breast cancer samples and their adjacent specimens using real-time PCR method Expression data was judged using Wilcoxon matched-pairs signed rank test. RESULTS: CYTOR level was higher in tumors compared with adjacent tissues. Nevertheless, there was no difference in expression of CDKN2B between these two sets of tissues. ROC curve analysis showed that CYTOR levels can differentiate between tumoral and adjacent tissues with AUC, specificity and sensitivity values of 0.65, 37% and 92% (P= 0.017). There was a positive correlation between expression levels of CYTOR and CDKN2B genes in breast cancer tissues (r= 0.5 and P= 0.0008) as well as adjacent tissues (r= 0.79 and P< 0.0001). Relative expression level of CDKN2B in normal tissues was associated with clinical stage (P= 0.014). Moreover, relative expression level of CDKN2B in tumor tissues was associated with the body weight. There was no other association between expressions of CYTOR and CDKN2B and clinical or pathological variables. CONCLUSIONS: Cumulatively, this study offers evidence for involvement of these genes in the pathoetiology of breast cancer.

Corrigendum to "Protective effects of chlorogenic acid against ionizing radiation-induced testicular toxicity" [Heliyon 8 (10) (October 2022) Article e10798].

[This corrects the article DOI: 10.1016/j.heliyon.2022.e10798.].

Interactions between non-coding RNAs and HIF-1α in the context of cancer.

Hypoxia-inducible factor 1α (HIF-1α) is a subunit of the HIF-1 transcription factor which is encoded by the HIF1A gene. This transcription factor is the main modulator of the cell response to hypoxia. Hypoxia-induced up-regulation of HIF-1α is involved in the pathogenesis of cancer. Recently, the interactions of several long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs) with HIF-1α have been reported. These ncRNAs regulate the expression of HIF-1α through different mechanisms. The regulatory roles of ncRNAs on HIF-1α are involved in the response of cancer cells to a wide range of anticancer drugs such as sorafenib, cisplatin, propofol, doxorubicin, and paclitaxel. Therefore, identification of the complex network between ncRNAs and HIF-1α not only facilitates the design of novel therapies but also promotes the efficacy of conventional anticancer treatments. This review aims to explain the interactions between these classes of ncRNAs and HIF-1α in the context of cancer.

Expression of NF-κB-associated lncRNAs in different types of migraine.

PURPOSE: NF-κB partakes in the pathophysiology of neurologic conditions. We quantified levels of NF-κB-associated genes in 119 patients with migraine versus healthy controls. METHODS: We measured levels of NF-κB-associated genes in 42 patients with migraine compared with age- and sex-matched controls. RESULTS: Comparison between patients without aura and controls revealed down-regulation of PACER [expression ratio (95% CI) 0.15 (0.06-0.36), P value < 0.0001]. Similar results were detected when comparing expression of PACER in patients with aura and controls [expression ratio (95% CI) 0.05 (0.02-0.12), P value < 0.0001]. Both DILC and CEBPA were over-expressed in patients with aura [expression ratio (95% CI) 4.9 (2.96-7.83), P value < 0.0001 and expression ratio (95% CI) 3.65 (2.39-5.24), P value < 0.0001, respectively] and in patients without aura compared with controls [expression ratio (95% CI) 3.6 (2.21-5.69), P value < 0.0001 and expression ratio (95% CI) 4.5 (2.53-7.11), P value < 0.0001, respectively]. ADINR was over-expressed in patients with aura [expression ratio (95% CI) 4.98 (3.09-8.33), P value < 0.0001] as well as patients without aura compared with controls [expression ratio (95% CI) 13.15 (7.41-23.58), P value < 0.0001]. Notably, ADINR levels were lower in patients with aura compared with patients without aura. When comparing ATG5 levels in patients with aura and controls, significant up-regulation was detected [expression ratio (95% CI) 4.4 (3.01-6.32), P value < 0.0001]. This pattern was also detected in patients without aura compared with controls [expression ratio (95% CI) 3.5 (2.28-5.35), P < 0.0001]. Finally, expression of DICER1-AS1 was elevated in patients with aura compared with patients without aura [expression ratio (95% CI) 2.47 (1.14-5.85), P = 0.03]. This lncRNA was under-expressed in patients without aura compared with controls [expression ratio (95% CI) 0.4 (0.21-1.31), P = 0.03]. CEBPA, ATG5 and ADINR had the best AUC values for distinguishing patients with aura from controls (AUC values = 0.91, 0.85 and 0.83, respectively). The AUC values for separation between patients without aura and controls were 0.90, 0.86 and 0.75 for CEBPA, ATG5 and ADINR, respectively. CONCLUSION: Taken together, several genes in the NF-κB pathway has been revealed to be dysregulated in migraineurs and expression of these genes can be used as markers for this neurological condition.

NLRP3: Role in ischemia/reperfusion injuries.

NLR family pyrin domain containing 3 (NLRP3) is expressed in immune cells, especially in dendritic cells and macrophages and acts as a constituent of the inflammasome. This protein acts as a pattern recognition receptor identifying pathogen-associated molecular patterns. In addition to recognition of pathogen-associated molecular patterns, it recognizes damage-associated molecular patterns. Triggering of NLRP3 inflammasome by molecules ATP released from injured cells results in the activation of the inflammatory cytokines IL-1ß and IL-18. Abnormal activation of NLRP3 inflammasome has been demonstrated to stimulate inflammatory or metabolic diseases. Thus, NLRP3 is regarded as a proper target for decreasing activity of NLRP3 inflammasome. Recent studies have also shown abnormal activity of NLRP3 in ischemia/reperfusion (I/R) injuries. In the current review, we have focused on the role of this protein in I/R injuries in the gastrointestinal, neurovascular and cardiovascular systems.

Protective effects of chlorogenic acid against ionizing radiation-induced testicular toxicity.

Background: Testicular tissues could damage by ionizing radiation (IR) during the treatment of pelvic cancers. The aim of this study was to investigate both the protective and therapeutic effects of chlorogenic acid (CGA) on IR-induced mouse testis tissue damage. Methods: In this experimental study, 70 mice were divided into 3 groups, including group 1 (normal saline), group 2 (IR + normal saline), and group 3 (IR + 5, 10, 20, 40, and 80 mg/kg) CGA via I.P injection. Animals in groups 2 and 3 received a dose of 2.0 Gy total-body irradiation in a single fraction. At two determined time points (16 h and 35 days after exposure), the testis and caudal part of both epididymis were isolated and underwent subsequent analyses. Results: The results showed that irradiation of mice caused massive damage to spermatogenesis, seminiferous tubules, basal lamina, Leydig cells, and sperm parameters. Further biochemical assessment of the data demonstrated that 40 mg/kg CGA almost restored MDA to a normal level. In addition, the level of SOD, TAC, and GSH were significantly increased in the 40 mg/kg CGA treated group. Molecular evidence confirmed the protective effects of CGA and also revealed that the ratio of Bax/Bcl-2 in the presence of 40 mg/kg CGA was significantly decreased compared to IR and some treated groups. Conclusion: The protective and therapeutic effects of CGA on testis were found to be positively correlated with the dose level.

Implication of non-coding RNA-mediated ROCK1 regulation in various diseases.

Rho Associated Coiled-Coil Containing Protein Kinase 1 (ROCK1) is a protein serine/threonine kinase which is activated upon binding with the GTP-bound form of Rho. This protein can modulate actin-myosin contraction and stability. Moreover, it has a crucial role in the regulation of cell polarity. Therefore, it participates in modulation of cell morphology, regulation of expression of genes, cell proliferation and differentiation, apoptotic processes as well as oncogenic processes. Recent studies have highlighted interactions between ROCK1 and several non-coding RNAs, namely microRNAs, circular RNAs and long non-coding RNAs. Such interactions can be a target of medications. In fact, it seems that the interactions are implicated in therapeutic response to several medications. In the current review, we aimed to explain the impact of these interactions in the pathoetiology of cancers as well as non-malignant disorders.

Molecular mechanisms of inhibitor of growth (ING) family members in health and malignancy.

ING genes belong to family of tumor suppressor genes with regulatory functions on cell proliferation, apoptosis, and cellular senescence. These include a family of proteins with 5 members (ING1-5), which are downregulated in human malignancies and/or affected by pathogenic mutations. ING proteins are highly evolutionarily conserved proteins containing several domains through which bind to chromatin structures by exerting their effects as readers of histone modification marks, and also binding to proteins like p53 involved in biological processes such as cell cycle regulation. Further, they are known as subunits of histone acetylation as well as deacetylation complexes and so exert their regulatory roles through epigenetic mechanisms. Playing role in restriction of proliferative but also invasive potentials of normal cells, INGs are particularly involved in cancer development and progression. However, additional studies and experimental confirmation are required for these models. This paper highlights the potential impact that INGs may have on the development of human cancer and explores what new information has recently arise on the functions of ING genes.

Role of PI3K/AKT pathway in squamous cell carcinoma with an especial focus on head and neck cancers.

PI3K/AKT pathway is an important pathway in the carcinogenesis since it has central impacts in the regulation of metabolic pathways, cell proliferation and survival, gene expression and protein synthesis. This pathway has been reported to be dysregulated in several types of cancers. In the current review, we summarize the role of this signaling pathway in squamous cell carcinomas (SCCs) originated from different parts of body cervix, oral cavity, head and neck and skin. The data presented in the current review shows the impact of dysregulation of PI3K/AKT pathway in survival of patients with SCC. Moreover, targeted therapies against this pathway have been found to be effective in reduction of tumor burden both in animal models and clinical settings. Finally, a number of molecules that regulate PI3K/AKT pathway can be used as diagnostic markers for different types of SCCs.

The interaction between human papilloma viruses related cancers and non-coding RNAs.

Human papillomaviruses (HPVs) constitute a number of double-stranded DNA viruses with propensity to cause infection in squamous epithelial cells. Certain types of these viruses have been found to cause human cancers through delivering their oncoproteins E6 and E7. Since not all of infected patients develop malignant lesions, other factors might affect HPV-associate carcinogenic processes. A number of investigations have shown interaction between HPV-encoded proteins and a number of non-coding RNAs, principally microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Such interactions have been found to influence pathogenesis of HPV-related cancers. miR-21, miR-9, miR-143, miR-214 and let-7 are among miRNAs that contribute in the pathogenesis of HPV-related lesions. HOTAIR, SNHG8, SOX2OT, SNHG12, GABPB1-AS1, SOX21-AS1, DINO, HOST2, CCDST, FAM83H-AS1, TMPOP2 and CCEPR are examples of lncRNAs that contribute in this process. In the current review, we provide an outline of investigations that reported the impact of these transcripts in HPV-related cancers.

Interaction between non-coding RNAs, mRNAs and G-quadruplexes.

G-quadruplexes are secondary helical configurations established between guanine-rich nucleic acids. The structure is seen in the promoter regions of numerous genes under certain situations. Predicted G-quadruplex-forming sequences are distributed across the genome in a non-random way. These structures are formed in telomeric regions of the human genome and oncogenic promoter G-rich regions. Identification of mechanisms of regulation of stability of G-quadruplexes has practical significance for understanding the molecular basis of genetic diseases such as cancer. A number of non-coding RNAs such as H19, XIST, FLJ39051 (GSEC), BC200 (BCYRN1), TERRA, pre-miRNA-1229, pre-miRNA-149 and miR-1587 have been found to contain G-quadraplex-forming regions or affect configuration of these structures in target genes. In the current review, we outline the recent research on the interaction between G-quadruplexes and non-coding RNAs, other RNA transcripts and DNA molecules.

Aberrant expression of miRNAs in epilepsy.

Epilepsy is manifested by intermittent convulsions and alterations in consciousness. This disorder has serious effects on daily functions and physical and mental health of affected patients. A variety of temporary irregularities in the function of brain can results in epilepsy. The molecular mechanism of epilepsy and the underlying causes of abnormal apoptotic responses in neurons, dysregulation of regenerative mechanisms in glial cells and abnormal immune reactions in the context of epilepsy are not clear. microRNAs (miRNAs) as important regulators of cell apoptosis as well as regenerative and immune responses have been shown to affect pathologic events in epilepsy. In the current review, we aimed at defining the role of miRNAs in the pathophysiology of epilepsy. We have listed dysregulated miRNAs in animal models of epilepsy and human subjects. miR-25-3p, miR-494, miR-139-5p, miR-101a-3p, miR-344a, miR-129, miR-298 and miR-187 are among down-regulated miRNAs in epilepsy. Moreover, expressions of miR-132, miR-146a, miR-181a and miR-155 have been reported to be increased in epilepsy. A number of genetic variants within miRNAs can affect risk of epilepsy. We discuss the role of miRNAs in the development of epilepsy.

Association analysis of MALAT1 polymorphisms and risk of psoriasis among Iranian patients.

MALAT1 is a long non-coding transcript that affects immune reactions, thus being involved in the pathoaetiology of immune-related conditions. We investigated the associations between two genetic variants in MALAT1 and susceptibility to psoriasis in the Iranian population. The G allele of rs619586 has been shown to be less common among cases versus controls (odds ratios (OR; 95% confidence intervals (CI)) = 0.57 (0.36-0.9)), adjusted p = .02). This single nucleotide polymorphism has been associated with the risk of psoriasis in a dominant model (AG + GG vs. AA: OR (95% CI) = 0.56 (0.35-0.92), adjusted p = .04) as well as log-additive model (OR (95% CI) = 0.59 (0.38-0.92), adjusted p = .04). The rs3200401 was not associated with psoriasis in any of the supposed inheritance models. This study potentiates rs619586 as a risk locus for psoriasis in the Iranian population.

Emerging role of non-coding RNAs in the course of HIV infection.

Recent studies have shown that non-coding region of the human genome can exert important regulatory roles on critical biological functions, including response to viral infections, among them is human immunodeficiency virus (HIV). HIV/AIDS is characterized by a gradual diminution of CD4 + T cells resulting in progressive deterioration of host immune responses and eventually high vulnerability to opportunistic infections and cancer. T cells functions have been shown to be delicately regulated by an active functional network of non-coding RNAs. Several lncRNAs such as MALAT1, NEAT1, GAS5, LOC102549805, NKILA, BACE1-AS, LINC00313, RP11-539L10.2, PVT1, LINC00173, NRON and AK130181 have been found to affect response of immune system to HIV or its pathological consequences. Moreover, numerous miRNAs such as hsa-miR-191-5p, miR-155, miR-103, miR-107, miR-150, miR-144, miR-125b, miR-146a, miR-146b-5p and miR-15a are involved in this process. In the current manuscript, we explain the role of lncRNAs and miRNAs in the regulation of response to HIV infection, apoptosis and activity of T cells, reactivation or latency of this virus and even pathological manifestations such as Tat-mediated induction of astrocytic amyloidosis.

The Emerging Role of Non-Coding RNAs in Osteoarthritis.

Osteoarthritis (OS) is the most frequent degenerative condition in the joints, disabling many adults. Several abnormalities in the articular cartilage, subchondral bone, synovial tissue, and meniscus have been detected in the course of OA. Destruction of articular cartilage, the formation of osteophytes, subchondral sclerosis, and hyperplasia of synovial tissue are hallmarks of OA. More recently, several investigations have underscored the regulatory roles of non-coding RNAs (ncRNAs) in OA development. Different classes of non-coding RNAs, including long ncRNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), have been reported to affect the development of OA. The expression level of these transcripts has also been used as diagnostic tools in OA. In the present article, we aimed at reporting the role of these transcripts in this process. We need to give a specific angle on the pathology to provide meaningful thoughts on it.

The Emerging Role of Non-Coding RNAs in Pituitary Gland Tumors and Meningioma.

Long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs) are non-coding transcripts which are involved in the pathogenesis of pituitary gland tumors. LncRNAs that participate in the pathogenesis of pituitary gland tumors mainly serve as sponges for miRNAs. CLRN1-AS1/miR-217, XIST/miR-424-5p, H19/miR-93a, LINC00473/miR-502-3p, SNHG7/miR-449a, MEG8/miR-454-3p, MEG3/miR-23b-3p, MEG3/miR-376B-3P, SNHG6/miR-944, PCAT6/miR-139-3p, lncRNA-m433s1/miR-433, TUG1/miR-187-3p, SNHG1/miR-187-3p, SNHG1/miR-302, SNHG1/miR-372, SNHG1/miR-373, and SNHG1/miR-520 are identified lncRNA/miRNA pairs that are involved in this process. Hsa_circ_0001368 and circOMA1 are two examples of circRNAs that contribute to the pathogenesis of pituitary gland tumors. Meanwhile, SNHG1, LINC00702, LINC00460, and MEG3 have been found to partake in the pathogenesis of meningioma. In the current review, we describe the role of non-coding RNAs in two types of brain tumors, i.e., pituitary tumors and meningioma.

Expression Analysis of NF-κB-Related lncRNAs in Parkinson's Disease.

Parkinson's disease (PD) has been shown to affect approximately 1% of the persons aged more than 65 years. This multifactorial disorder has been associated with abnormal function of NF-κB signals. In this research, we have evaluated expressions of NF-κB-related long non-coding RNAs in the circulation of PD patients compared with healthy controls. Expression of PACER was lower in total PD patients compared with healthy persons (Ratio of mean expressions (RME)=0.32, P value<0.001). This pattern was also evident among males (RME=0.25, P value<0.001). Expression of DILC was higher in total PD patients (RME=4.07, P value<0.001), and in both sex-based subgroups (RME=3.77, P value=0.01 and RME=4.25, P value<0.001, for females and males, respectively). Similarly, CEBPA was significantly over-expressed in total PD patients (RME=14.76, P value<0.001), and in both sex-based subgroups (RME=12.42, P value<0.001 and RME=15.80, P value<0.001, for females and males, respectively). ATG5 had a similar expression pattern (RME=2.6, P value=1E-08, RME=1.73, P value=0.03 and RME=3.09, P value=1E-07, for total cases, females and males, respectively). H19 was up-regulated in total cases and male cases compared with corresponding controls (RME=2.19, P value<0.001, RME=2.68, P value=0.01, respectively). Finally, HNFA1-AS was down-regulated in all comparisons (RME=0.10, P value=2E-06, RME=0.08, P value<0.001 and RME=0.12, P value<0.001, for total cases, females and males, respectively). Among PD patients, expressions of NKILA and ADINR were robustly correlated with each other (r=0.75, P value=2.40E-10). In addition, expression levels of DICER1-AS were significantly correlated with those of ADINR, PACER and H19 in these patients (r=0.73, P value=1.76E-9; r=0.72, P value=5.15E-09 and r=0.72, P value=3.09E-09, respectively). Correlation analyses among healthy controls revealed robust correlations between CHAST and CEBPA (r=0.84, P value=3.09E-09), NKILA and ADINR (r=0.80, P value=4.24E-12) as well as between DILC and CHAST (r=0.76, P value=1.70E-10). CEBPA had the best parameters among all assessed genes (AUC=0.96, Sensitivity=0.90 and specificity=0.97). DILC and ATG5 were the most appropriate markers after CEBPA with AUC values of 0.82 and 0.80, respectively. Most notably, combination of all genes improved AUC, sensitivity and specificity parameters to 1, 0.97 and 0.99, respectively. Cumulatively, the current study provides evidence for participation of NF-κB-related lncRNAs in the pathoetiology of PD.

Contribution of miRNAs in the Pathogenesis of Breast Cancer.

Breast cancer is the most frequently diagnosed cancer among females. Gene expression profiling methods have shown the deregulation of several genes in breast cancer samples and have confirmed the heterogeneous nature of breast cancer at the genomic level. microRNAs (miRNAs) are among the recently appreciated contributors in breast carcinogenic processes. These small-sized transcripts have been shown to partake in breast carcinogenesis through modulation of apoptosis, autophagy, and epithelial-mesenchymal transition. Moreover, they can confer resistance to chemotherapy. Based on the contribution of miRNAs in almost all fundamental aspects of breast carcinogenesis, therapeutic intervention with their expression might affect the course of this disorder. Moreover, the presence of miRNAs in the peripheral blood of patients potentiates these transcripts as tools for non-invasive diagnosis of breast cancer.

Investigation of FADS Gene Cluster Single Nucleotide Polymorphisms in End-Stage Renal Disease Compared With Normal Controls.

End-stage renal disease (ESRD) is a public health problem with a high burden. The condition is associated with abnormalities in lipid metabolism. The fatty acid desaturase (FADS) gene cluster includes three genes that are significantly correlated with a number of pathologic conditions related to abnormal lipid levels. In the current study, we genotyped rs174556, rs99780, and rs7115739 single nucleotide polymorphisms within the FADS cluster in a population of ESRD patients and healthy controls. The rs174556 of the FADS1 gene and rs99780 of the FADS2 gene were not associated with the risk of ESRD in any inheritance model. However, the rs7115739 of FADS3 was associated with the risk of ESRD in all models except for the recessive model. The T allele of this SNP was significantly less prevalent among cases compared with controls [odds ratio (OR) (95% CI) = 0.44 (0.25-0.77), P value = 0.004]. GT and TT genotypes has been shown to decrease the risk of ESRD in a codominant model [OR (95% CI) = 0.49 (0.26-0.92) and OR (95% CI) = 0.18 (0.02-1.6), respectively; P value = 0.019]. In the dominant model, GT + TT status was associated with lower risk of ESRD [OR (95% CI) = 0.45 (0.24-0.82), P value = 0.0078]. Assessment of association between this SNP and risk of ESRD in an overdominant model revealed that GT genotype decreases the risk of this condition [OR (95% CI) = 0.5 (0.27-0.94), P value = 0.029]. Taken together, the rs7115739 of FADS3 is suggested as a putative modulator of the risk of ESRD in the Iranian population.

Non-coding RNA Activated by DNA Damage: Review of Its Roles in the Carcinogenesis.

Long intergenic non-coding RNA 00657 (LINC00657) or "non-coding RNA activated by DNA damage" (NORAD) is an extremely conserved and copious long non-coding RNA (lncRNA). This transcript has pivotal role in the preservation of genome integrity. Several researches have appraised the role of NORAD in the evolution of human cancers with most of them indicating an oncogenic role for this lncRNA. Several miRNAs such as miR-199a-3p, miR-608, miR-155-5p, miR-590-3p, miR-495-3p, miR-608, miR-202-5p, miR-125a-3p, miR-144-3p, miR-202-5p, and miR-30a-5p have been recognized as targets of NORAD in different cancer cell lines. In addition, NORAD has interactions with cancer-related pathways, particularly STAT, TGF-ß, Akt/mTOR, and PI3K/AKT pathway. Over-expression of NORAD has been related with poor clinical outcome of patients with diverse types of neoplasms. Collectively, NORAD is a prospective marker and target for combating cancer.