Publications by authors named "Bashdar Mahmud Hussen"

103 Publications

Gasotransmitters in the tumor microenvironment: Impacts on cancer chemotherapy (Review).

Mol Med Rep 2022 Jul 26;26(1). Epub 2022 May 26.

General Directorate of Scientific Research Center, Salahaddin University‑Erbil, Erbil, Kurdistan Region 44002, Iraq.

Nitric oxide, carbon monoxide and hydrogen sulfide are three endogenous gasotransmitters that serve a role in regulating normal and pathological cellular activities. They can stimulate or inhibit cancer cell proliferation and invasion, as well as interfere with cancer cell responses to drug treatments. Understanding the molecular pathways governing the interactions between these gases and the tumor microenvironment can be utilized for the identification of a novel technique to disrupt cancer cell interactions and may contribute to the conception of effective and safe cancer therapy strategies. The present review discusses the effects of these gases in modulating the action of chemotherapies, as well as prospective pharmacological and therapeutic interfering approaches. A deeper knowledge of the mechanisms that underpin the cellular and pharmacological effects, as well as interactions, of each of the three gases could pave the way for therapeutic treatments and translational research.
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http://dx.doi.org/10.3892/mmr.2022.12749DOI Listing
July 2022

Angiotensin I converting enzyme gene polymorphisms and risk of psychiatric disorders.

BMC Psychiatry 2022 May 23;22(1):351. Epub 2022 May 23.

Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Angiotensin-converting enzyme (ACE) as an important enzyme in the renin-angiotensin system facilitates biogenesis of the functionally active product angiotensin II from angiotensin I. ACE gene contains a number of functional polymorphisms which modulate activity of the encoded protein. In the current case-control study, we appraised the association between the rs4359 and rs1799752 polymorphisms and risk of bipolar disorder (type I and type II; BPDI and BPDII), schizophrenia (SCZ) and obsessive-compulsive disorder (OCD). The rs4359 was associated with risk of OCD, BPDI and BPDII in co-dominant and dominant models. The rs1799752 was associated with all assessed psychiatric conditions in four inheritance models except for BPDII whose association was not significant in recessive model. The I allele of rs1799752 was associated with OCD (adjusted FDR q-Value = 4.04E-04), SCZ (adjusted FDR q-Value = 6.00E-06), BPDI (adjusted FDR q-Value = 8.40E-03) and BPDII (adjusted FDR q-Value = 6.00E-06). The effective T allele of rs4359 showed a significant association with disease risk for BPDII group. The estimated haplotypes of these polymorphisms have been distributed differently among patients and controls. Taken together, ACE polymorphisms can be regarded as risk factors for a variety of psychiatric disorders.
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http://dx.doi.org/10.1186/s12888-022-04007-wDOI Listing
May 2022

A review on the role of DANCR in the carcinogenesis.

Cancer Cell Int 2022 May 19;22(1):194. Epub 2022 May 19.

Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

DANCR is an RNA gene located on chr4. This gene has several splice variants. Up-regulation of DANCR has been reported in many types of cancers. This lncRNA is mainly located in the cytoplasm and regulates genes expression at post-transcriptional level. In fact, it acts as a molecular sponge for a variety of miRNAs, including miR-874-3P, miR-335, miR-149, miR-4319, miR-758-3p, miR-216a-5p, miR-874-3p, miR-33a-5p, miR-335-5p, miR-145-3p, miR-665, miR-345-5p and miR-125b-5p. DANCR also regulates activity of PI3K/AKT/NF-κB, Wnt/β-catenin, ERK/SMAD, MAPK, IL-6/JAK1/STAT3, Smad2/3, p53, FAK/PI3K/AKT/GSK3β/Snail pathways. In the current narrative review article, we summarize the roles of DANCR in the carcinogenesis, with an especial emphasis on its role in the development of osteosarcoma and lung, liver, pancreatic and colorectal cancers.
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http://dx.doi.org/10.1186/s12935-022-02612-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9118872PMC
May 2022

A Comprehensive Review on Function of miR-15b-5p in Malignant and Non-Malignant Disorders.

Front Oncol 2022 2;12:870996. Epub 2022 May 2.

Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

miR-15b-5p is encoded by gene. This gene is located on cytogenetic band 3q25.33. This miRNA participates in the pathogenesis of several cancers as well as non-malignant conditions, such as abdominal aortic aneurysm, Alzheimer's and Parkinson's diseases, cerebral ischemia reperfusion injury, coronary artery disease, dexamethasone induced steatosis, diabetic complications and doxorubicin-induced cardiotoxicity. In malignant conditions, both oncogenic and tumor suppressor impacts have been described for miR-15b-5p. Dysregulation of miR-15b-5p in clinical samples has been associated with poor outcome in different kinds of cancers. In this review, we discuss the role of miR-15b-5p in malignant and non-malignant conditions.
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http://dx.doi.org/10.3389/fonc.2022.870996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108330PMC
May 2022

Interaction Between Non-Coding RNAs and Interferons: With an Especial Focus on Type I Interferons.

Front Immunol 2022 27;13:877243. Epub 2022 Apr 27.

Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Interferons (IFNs) are a group of cellular proteins with critical roles in the regulation of immune responses in the course of microbial infections. Moreover, expressions of IFNs are dysregulated in autoimmune disorders. IFNs are also a part of immune responses in malignant conditions. The expression of these proteins and activities of related signaling can be influenced by a number of non-coding RNAs. IFN regulatory factors (IRFs) are the most investigated molecules in the field of effects of non-coding RNAs on IFN signaling. These interactions have been best assessed in the context of cancer, revealing the importance of immune function in the pathoetiology of cancer. In addition, IFN-related non-coding RNAs may contribute to the pathogenesis of neuropsychiatric conditions, systemic sclerosis, Newcastle disease, Sjögren's syndrome, traumatic brain injury, lupus nephritis, systemic lupus erythematosus, diabetes mellitus, and myocardial ischemia/reperfusion injury. In the current review, we describe the role of microRNAs and long non-coding RNAs in the regulation of IFN signaling.
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http://dx.doi.org/10.3389/fimmu.2022.877243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9091820PMC
May 2022

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

Pathol Res Pract 2022 Jun 7;234:153939. Epub 2022 May 7.

Department of Pathology, Shohada-e-Tajrish Educational Hospital, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

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.
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http://dx.doi.org/10.1016/j.prp.2022.153939DOI Listing
June 2022

Interplay between PI3K/AKT pathway and heart disorders.

Mol Biol Rep 2022 May 2. Epub 2022 May 2.

Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

The PI3K/AKT signaling has crucial role in the regulation of numerous physiological functions through activation of downstream effectors and modulation of cell cycle transition, growth and proliferation. This pathway participates in the pathogenesis of several human disorders such as heart diseases through regulation of size and survival of cardiomyocytes, angiogenic processes as well as inflammatory responses. Moreover, PI3K/AKT pathway participates in the process of myocardial injury induced by a number of substances such as HO, Mercury, lipopolysaccharides, adriamycin, doxorubicin and epirubicin. In this review, we describe the contribution of this pathway in the pathoetiology of myocardial ischemia/reperfusion injury and myocardial infarction, heart failure, cardiac hypertrophy, cardiomyopathy and toxins-induced cardiac injury.
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http://dx.doi.org/10.1007/s11033-022-07468-0DOI Listing
May 2022

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

Cancer Cell Int 2022 Apr 29;22(1):171. Epub 2022 Apr 29.

School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia.

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.
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http://dx.doi.org/10.1186/s12935-022-02601-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9052686PMC
April 2022

Emerging role of circular RNAs in the pathogenesis of ovarian cancer.

Cancer Cell Int 2022 Apr 29;22(1):172. Epub 2022 Apr 29.

Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Ovarian cancer is a female malignancy with high fatality-to-case ratio, which is due to late detection of cancer. Understanding the molecular mechanisms participating in these processes would facilitate design of therapeutic modalities and identification of novel tumor markers. Recent investigations have shown contribution of circular RNAs (circRNAs) in the evolution of ovarian cancer. These transcripts are produced through a back-splicing mechanism. The enclosed configuration of circRNAs protects them from degradation and potentiates them as biomarkers. Several circRNAs such as circMUC16, circRNA_MYLK, circRNA-UBAP2, circWHSC1, hsa_circ_0013958, circFGFR3, hsa_circRNA_102958 and circ_0072995 have been found to be up-regulated in this cancer, acting as oncogenes. On the other hand, circ-ITCH, circPLEKHM3, circ_100395, circ_0078607, circATRNL1, circHIPK3, circRHOBTB3, circEXOC6B, circ9119 and CDR1as are among down-regulated circRNAs in ovarian cancer. Expression levels of circCELSR1, circ_CELSR1, circATL2, circNRIP1, circTNPO3 and hsa_circ_0000714 have been shown to affect resistance of ovarian cancer cells to chemotherapy. Moreover, circ_100395, circFGFR3, circ_0000554, circCELSR1, circ-PTK2, circLNPEP, circ-CSPP1, circ_0000745, circ_100395 and circPLEKHM3 have been shown to regulate epithelial-mesenchymal transition and metastatic ability of ovarian cancer cells. In the current review, we explain the roles of circRNAs in the evolution and progression of ovarian cancer.
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http://dx.doi.org/10.1186/s12935-022-02602-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9052556PMC
April 2022

Expression analysis of vitamin D receptor and its related long non-coding RNAs in peripheral blood of patients with Parkinson's disease.

Mol Biol Rep 2022 Apr 15. Epub 2022 Apr 15.

Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Parkinson's disease (PD) is a neurological condition that is associated with abnormal expression of several transcripts. Vitamin D receptor (VDR) is a possible participant in the pathogenesis of PD.

Methods And Results: In the present research project, we evaluated expressions of VDR and three functionally associated long non-coding RNAs with this signaling, namely SNHG6, SNHG16 and LINC00346 in PD patients versus normal controls. Level of SNHG6 transcripts was lower in total patients in comparison with total controls (Expression ratio (95% CI) 0.44 (0.17-1.08)) and in male patients compared with male controls (Expression ratio (95% CI) 0.29 (0.13-0.65)). On the other hand, expression of VDR was higher in total patients compared with total controls (Expression ratio (95% CI) 10.86 (4.37-26.72)) and in male patients compared with male controls (Expression ratio (95% CI) 22.16 (6.23-78.8)). There was no significant difference in expression of SNHG16 and LINC00346 between PD patients and controls. Amounts of SNHG6 and VDR transcripts could differentiate total PD patients from total controls with AUC values of 0.66 and 0.86, respectively.

Conclusions: Cumulatively, the results of the present investigation imply dysregulation of VDR signaling in PD and necessitate conduction of further functional studies.
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http://dx.doi.org/10.1007/s11033-022-07372-7DOI Listing
April 2022

Therapeutic Potential of Microvesicles in Cell Therapy and Regenerative Medicine of Ocular Diseases With an Especial Focus on Mesenchymal Stem Cells-Derived Microvesicles.

Front Genet 2022 29;13:847679. Epub 2022 Mar 29.

Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

These days, mesenchymal stem cells (MSCs), because of immunomodulatory and pro-angiogenic abilities, are known as inevitable factors in regenerative medicine and cell therapy in different diseases such as ocular disorder. Moreover, researchers have indicated that exosome possess an essential potential in the therapeutic application of ocular disease. MSC-derived exosome (MSC-DE) have been identified as efficient as MSCs for treatment of eye injuries due to their small size and rapid diffusion all over the eye. MSC-DEs easily transfer their ingredients such as miRNAs, proteins, and cytokines to the inner layer in the eye and increase the reconstruction of the injured area. Furthermore, MSC-DEs deliver their immunomodulatory cargos in inflamed sites and inhibit immune cell migration, resulting in improvement of autoimmune uveitis. Interestingly, therapeutic effects were shown only in animal models that received MSC-DE. In this review, we summarized the therapeutic potential of MSCs and MSC-DE in cell therapy and regenerative medicine of ocular diseases.
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http://dx.doi.org/10.3389/fgene.2022.847679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9001951PMC
March 2022

Interplay Between Non-Coding RNAs and Programmed Cell Death Proteins.

Front Oncol 2022 23;12:808475. Epub 2022 Mar 23.

Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti Universality of Medical Sciences, Tehran, Iran.

Programmed cell death (PDCD) family of proteins includes at least 12 members, function of seven of them being more investigated. These members are PDCD1, PDCD2, PDCD4, PDCD5, PDCD6, PDCD7 and PDCD10. Consistent with the important roles of these proteins in the regulation of apoptosis, dysregulation of PDCDs is associated with diverse disorders ranging from intervertebral disc degeneration, amyotrophic lateral sclerosis, immune thrombocytopenia, type 1 diabetes, congenital hypothyroidism, Alzheimer's disease to different types of cancers. More recently, the interaction between non-coding RNAs and different members of PDCD family is being discovered. In the current study, we described the functional interactions between PDCDs and two classes of non-coding RNAs, namely microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). miR-21 and miR-183 are two miRNAs whose interactions with PDCDs have been assessed in different contexts. The lncRNAs interaction with PDCDs is mainly assessed in the context of neoplasia indicating the role of MALAT1, MEG3, SNHG14 and LINC00473 in this process.
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http://dx.doi.org/10.3389/fonc.2022.808475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8983884PMC
March 2022

The Emerging Roles of the β-Secretase BACE1 and the Long Non-coding RNA BACE1-AS in Human Diseases: A Focus on Neurodegenerative Diseases and Cancer.

Front Aging Neurosci 2022 21;14:853180. Epub 2022 Mar 21.

Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

The β-Secretase (BACE1) is widely studied to be particularly involved in amyloid deposition, a process known as the pathogenic pathway in neurodegenerative diseases. Therefore, BACE1 expression is frequently reported to be upregulated in brain samples of the patients with Alzheimer's disease (AD). BACE1 expression is regulated by BACE1-AS, a long non-coding RNA (lncRNA), which is transcribed in the opposite direction to its locus. BACE1-AS positively regulates the expression, and their expression levels are regulated in physiological processes, such as brain and vascular homeostasis, although their roles in the regulation of amyloidogenic process have been studied further. BACE1-AS dysregulation is reported consistent with BACE1 in a number of human diseases, such as AD, Parkinson's disease (PD), heart failure (HF), and mild cognitive impairment. BACE1 or less BACE1-AS inhibition has shown therapeutic potentials particularly in decreasing manifestations of amyloid-linked neurodegenerative diseases. Here, we have reviewed the role of lncRNA BACE1 and BACE1-AS in a number of human diseases focusing on neurodegenerative disorders, particularly, AD.
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http://dx.doi.org/10.3389/fnagi.2022.853180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8978056PMC
March 2022

Expression analysis of IFNAR1 and TYK2 transcripts in COVID-19 patients.

Cytokine 2022 May 4;153:155849. Epub 2022 Mar 4.

Critical Care Quality Improvement Research Center, Loghman Hakin Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Critical Care Fellowship, Department of Anesthesiology, Shahid Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

As a member of JAK family of non-receptor tyrosine kinases, TYK2 has a crucial role in regulation of immune responses. This protein has a crucial role in constant expression of IFNAR1 on surface of cells and initiation of type I IFN signaling. In the current study, we measured expression of IFNAR1 and TYK2 levels in venous blood samples of COVID-19 patients and matched controls. TYK2 was significantly down-regulated in male patients compared with male controls (RME = 0.34, P value = 0.03). Though, levels of TYK2 were not different between female cases and female controls, or between ICU-admitted and non-ICU-admitted cases. Expression of IFNAR1 was not different either between COVID-19 cases and controls or between patients required ICU admission and non-ICU-admitted cases. However, none of these transcripts can properly diffrentiate COVID-19 cases from controls or separate patients based on disease severity. The current study proposes down-regulation of TYK2 as a molecular mechanism for incapacity of SARS-CoV-2 in induction of a competent IFN response.
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http://dx.doi.org/10.1016/j.cyto.2022.155849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8894869PMC
May 2022

The Interaction Between Non-Coding RNAs and Calcium Binding Proteins.

Front Oncol 2022 4;12:848376. Epub 2022 Mar 4.

Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Calcium binding proteins (CBP) are a group of proteins mediating the effects of calcium on cellular functions. These proteins can regulate calcium levels inside the cells and contribute in several cellular functions through transporting this ion across cell membranes or decoding related signals. Recent studies have shown that several non-coding RNAs interact with CBPs to affect their expression or activity. The interactions between these transcripts and CBPs have implications in the pathoetiology of human disorders, including both neoplastic and non-neoplastic conditions. In the current review, we describe the interactions between three classes of non-coding RNAs (long non-coding RNAs, circular RNAs, and microRNAs) and a number of CBPs, particularly CAB39, S100A1, S100A4, S100A7 and S100P. This kind of interaction has been verified in different pathological contexts such as drug-induced cardiotoxicity, osteoblasts cytotoxicity, acute lung injury, myocardial ischemia/reperfusion injury, proliferative diabetic retinopathy, glomerulonephritis, as well as a wide array of neoplastic conditions.
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http://dx.doi.org/10.3389/fonc.2022.848376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8934394PMC
March 2022

Expression of BDNF-Associated lncRNAs in Parkinson's disease.

Metab Brain Dis 2022 Apr 19;37(4):901-909. Epub 2022 Mar 19.

Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Decreased level of neurotrophic factor brain-derived neurotrophic factor (BDNF) has been supposed to participate in the pathoetiology of Parkinson's disease (PD). However, the underlying mechanisms of its dysregulation and the functional network between this factor and other transcripts have not been elucidated. In the current study, we measured expressions of BDNF, and four related long non-coding RNAs, namely BDNF-AS, MIR137HG, MIAT and PNKY in blood of PD patients and normal controls to find their expression levels in these patients and propose a possible mechanism for dysregulation of BDNF in PD patients. Notably, we detected down-regulation of all transcripts in the circulation of PD patients compared with controls. There was no significant difference in expression of either gene between male and female PD patients or patients receiving L-Dopa versus those receiving other drugs. Expression of none of genes was correlated with age, disease duration, disease stage, MMSE or UPDRS. Dynamic principal component analysis showed that expression levels of these genes almost clearly separated samples collected from healthy controls and PD patients into their respective groups. This suggests that the observed lncRNAs differences are associated with the pathophysiology of PD, and these lncRNAs might constitute an important biomarker signature for PD.
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http://dx.doi.org/10.1007/s11011-022-00946-1DOI Listing
April 2022

The Role of Circular RNAs in the Carcinogenesis of Bladder Cancer.

Front Oncol 2022 28;12:801842. Epub 2022 Feb 28.

Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Circular RNAs (circRNAs) are a group of transcripts with enclosed configurations which can regulate gene expression. These transcripts have important roles in normal development and in the pathogenesis of disorders. Recent evidence has supported involvement of circRNAs in the development of bladder cancer. Several circRNAs such as circ_0058063, hsa-circRNA-403658, circPDSS1, circCASC15, circRNA-MYLK, and circRNA_103809 have been upregulated in bladder cancer samples. On the other hand, hsa_circ_0137606, BCRC-3, circFUT8, hsa_circ_001598, circSLC8A1, hsa_circ_0077837, hsa_circ_0004826, and circACVR2A are among downregulated circRNAs in bladder cancer. Numerous circRNAs have diagnostic or prognostic value in bladder cancer. In this review, we aim to outline the latest findings about the role of circRNAs in bladder cancer and introduce circRNAs for further investigations as therapeutic targets.
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http://dx.doi.org/10.3389/fonc.2022.801842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8918517PMC
February 2022

DLX6-AS1: A Long Non-coding RNA With Oncogenic Features.

Front Cell Dev Biol 2022 25;10:746443. Epub 2022 Feb 25.

Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Long non-coding RNAs (lncRNAs) are a heterogeneous group of ncRNAs with characteristic size of more than 200 nucleotides. An increasing number of lncRNAs have been found to be dysregulated in many human diseases particularly cancer. However, their role in carcinogenesis is not precisely understood. DLX6-AS1 is an lncRNAs which has been unveiled to be up-regulated in various number of cancers. In different cell studies, DLX6-AS1 has shown oncogenic role promoting oncogenic phenotype of cancer cell lines. Increase in tumor cell proliferation, migration, invasion, and EMT while suppressing apoptosis in cancer cells are the effects of DLX6-AS1 in development and progression of cancer. In the majority of cell experiment, mediator miRNAs have been identified which are sponged and negatively regulated by DLX6-AS1, and they in turn regulate expression of a number of transcription factors, eventually affecting signaling pathways involved in carcinogenesis. These pathways form axes through which DLX6-AS1 promotes carcinogenicity of cancer cells. Xenograft animal studies, also have confirmed enhancing effect of DLX6-AS1 on tumor growth and metastasis. Clinical evaluations in cancerous patients have also shown increased expression of DLX6-AS1 in tumor tissues compared to healthy tissues. High DLX6-AS1 expression has shown positive association with advanced clinicopathological features in cancerous patients. Survival analyses have demonstrated correlation between high DLX6-AS1 expression and shorter survival. In cox regression analysis, DLX6-AS1 has been found as an independent prognostic factor for patients with various types of cancer.
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http://dx.doi.org/10.3389/fcell.2022.746443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8916230PMC
February 2022

Abnormal pattern of vitamin D receptor-associated genes and lncRNAs in patients with bipolar disorder.

BMC Psychiatry 2022 03 12;22(1):178. Epub 2022 Mar 12.

Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Bipolar disorder (BD) is a multifactorial condition. Several signaling pathways affect development of this disorder. With the purpose of exploring the role of vitamin D receptor (VDR) signaling in this disorder, we measured expression of selected mRNA coding genes and long non-coding RNAs (lncRNAs) in this pathway in patients versus normal subjects.

Methods: We measured expression of VDR-associated lncRNAs and mRNAs (SNHG6, MALAT1, Linc00511, Linc00346, VDR and CYP27B1) in the peripheral blood of BD patients vs. healthy individuals.

Results: Expression of SNHG6 was significantly higher in cases vs. controls (Posterior beta = 1.29, P value < 0.0001. Subgroup analysis by sex revealed significant results in both subgroups (P value < 0.0001 and P value = 0.023 for males and females, respectively). Expression of CYP27B1 was up-regulated in cases vs. controls (Posterior beta = 0.415, P < 0.0001). Such pattern was also detected among males (P < 0.0001), but not females (P = 0.419). Similarly, MALAT1 and Linc00346 were up-regulated in total cases vs. controls (Posterior beta = 0.694, P < 0.0001 and Posterior beta = 0.4, P = 0.012, respectively) and in male cases compared with male controls (Posterior beta = 0.712, P < 0.0001 and Posterior beta = 0.41, P value = 0.038, respectively). Expression of VDR was up-regulated in total cases compared with controls (Posterior beta = 0.683, P value = 0.001). Finally, expression of Linc00511 was not different between groups. MALAT1, SNHG6, CYP27B1, VDR and Linc00346 had AUC values of 0.95, 0.94, 0.91, 0.85 and 0.83 in differentiation of male patients from controls, respectively.

Conclusion: The current study suggests VDR-associated genes as possible markers for BD.
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http://dx.doi.org/10.1186/s12888-022-03811-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8918307PMC
March 2022

The role of circular RNAs in pancreatic cancer: new players in tumorigenesis and potential biomarkers.

Pathol Res Pract 2022 Apr 2;232:153833. Epub 2022 Mar 2.

Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Circular RNAs (circRNAs) are a newly identified class of non-coding RNAs (ncRNAs) which show different structure compared to other RNAs in terms of their covalently closed ends. To date, a huge number of circRNAs have been identified in various species and also several databases have been created for storing and providing accessibility to retrieved data on identified circRNAs. They are produced by back-splicing from mainly protein-coding genes. Same to other ncRNAs, circRNAs have been found to play role in gene regulation via interaction with other biomolecules like nucleic acids, proteins and microRNAs (miRNAs). They are involved in different physiological processes like vascular functions, brain and embryonic development, regulation of metabolism, cell cycle control and response to cellular stress. Dysregulation of circRNAs have been associated with many types of human diseases like cardiovascular diseases, immune diseases, neurologic diseases, diabetes and particularly various types of cancer. In this review, we have a look to the cellular experiments conducted on the role of circRNAs in the pancreatic cancer. Two cellular behaviors of two categories of circRNAs including up-regulated and down-regulated transcripts have been reviewed in pancreatic cancer. Furthermore, their potential application in diagnosis and prognosis of pancreatic cancer has been summarized. The results show circRNAs are potential diagnostic and prognostic biomarkers of pancreatic cancer.
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http://dx.doi.org/10.1016/j.prp.2022.153833DOI Listing
April 2022

Identification and Analysis of // Competing Endogenous RNA Axis in Late-Onset Alzheimer's Disease Using Bioinformatic and Experimental Approaches.

Front Aging Neurosci 2022 21;14:812169. Epub 2022 Feb 21.

Clinical Research Development Unit of Tabriz Valiasr Hospital, Tabriz University of Medical Sciences, Tabriz, Iran.

Alzheimer's disease (AD) is a heterogeneous degenerative brain disorder with a rising prevalence worldwide. () has emerged as one of the most intriguing new members of the SHISA family, in that, unlike other CKAMP counterparts, it exhibits a direct function in inhibitory synaptic GABAAR regulation. We used bioinformatics and experimental methods in this research to explore competing endogenous RNA (ceRNA) regulation of and in tau pathogenesis and their capacity as peripheral biomarkers linked to an abnormal inflammatory response in AD. The Gene Expression Omnibus database included two microarray datasets, including information on mRNAs (GSE106241) and miRNAs (GSE157239) from individuals with AD with different degrees of AD-associated neurofibrillary pathology in the temporal cortex (TC) tissue specimens and corresponding controls were downloaded from the Gene Expression Omnibus database. The limma package in the R software was used to identify differently expressed mRNAs (DEmRNAs) and miRNAs (DEmiRNAs) associated with AD-related neurofibrillary pathology. Additionally, we used the quantitative polymerase chain reaction technique to examine the expression of the // ceRNA axis in the peripheral blood (PB) of fifty AD patients and fifty control subjects. was shown to act as a ceRNA to control the expression throughout AD-associated neurofibrillary pathology in TC tissue specimens by sponging , based on our bioinformatics study. Furthermore, in PB specimens from individuals suffering from AD and normal controls, we found no substantial differences in expression patterns. expression in AD patients' PB was found to be reduced, as was the case in the TC. On the other hand, we discovered reduced amounts of in AD patients' PB samples compared to control subjects, unlike in TC tissue, where it had been demonstrated to be overexpressed. and expression levels showed a strong positive correlation, suggesting the presence of an interconnected network, most likely as a result of ceRNA regulation among PB specimens. The present study is the first evidence to highlight the expression of the // ceRNA axis in the brain and PB of AD patients, and offers a new viewpoint on molecular processes underlying AD pathogenic mechanisms.
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http://dx.doi.org/10.3389/fnagi.2022.812169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899724PMC
February 2022

Strategies to overcome the main challenges of the use of CRISPR/Cas9 as a replacement for cancer therapy.

Mol Cancer 2022 03 3;21(1):64. Epub 2022 Mar 3.

Institute of Human Genetics, Jena University Hospital, Jena, Germany.

CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats-associated protein 9) shows the opportunity to treat a diverse array of untreated various genetic and complicated disorders. Therapeutic genome editing processes that target disease-causing genes or mutant genes have been greatly accelerated in recent years as a consequence of improvements in sequence-specific nuclease technology. However, the therapeutic promise of genome editing has yet to be explored entirely, many challenges persist that increase the risk of further mutations. Here, we highlighted the main challenges facing CRISPR/Cas9-based treatments and proposed strategies to overcome these limitations, for further enhancing this revolutionary novel therapeutics to improve long-term treatment outcome human health.
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http://dx.doi.org/10.1186/s12943-021-01487-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8892709PMC
March 2022

The effects of Ginsenosides on PI3K/AKT signaling pathway.

Mol Biol Rep 2022 Feb 27. Epub 2022 Feb 27.

Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Ginsenosides belong to a group of steroid glycosides that are extracted from the plant genus Panax (ginseng). This plant has been used for a long time for the treatment of a variety of disorders in traditional medicine. Recent studies have assessed the biological impact of Ginsenosides in cell culture or animal models. Animal studies have shown their beneficial impacts in the remedy of pathological conditions in different tissues. The ameliorating effects of Ginsenosides in diverse pathogenic conditions can be attributed to their effects on the production of reactive oxygen species. These substances mainly affect the activity of AMPK/AKT and PI3K/AKT pathways. The beneficial effects of Ginsenosides have been appraised in diabetes-related complications, spinal cord injury, cerebral ischemia, myocardial ischemia, and other disorders which are associated with oxidative stress. Moreover, these substances have been shown to interfere with the pathologic conditions during carcinogenesis. In the current study, we explain these impacts in two distinct sections including non-neoplastic conditions and neoplastic conditions.
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http://dx.doi.org/10.1007/s11033-022-07270-yDOI Listing
February 2022

The emerging role non-coding RNAs in B cell-related disorders.

Cancer Cell Int 2022 Feb 22;22(1):91. Epub 2022 Feb 22.

Department of Pathology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Long non-coding RNAs and microRNAs have recently attained much attention regarding their role in the development of B cell lineage as well as participation in the lymphomagenesis. These transcripts have a highly cell type specific signature which endows them the potential to be used as biomarkers for clinical situations. Aberrant expression of several non-coding RNAs has been linked with B cell malignancies and immune related disorders such as rheumatoid arthritis, systemic lupus erythematous, asthma and graft-versus-host disease. Moreover, these transcripts can alter response of immune system to infectious conditions. miR-7, miR-16-1, miR-15a, miR-150, miR-146a, miR-155, miR-212 and miR-132 are among microRNAs whose role in the development of B cell-associated disorders has been investigated. Similarly, SNHG14, MALAT1, CRNDE, AL133346.1, NEAT1, SMAD5-AS1, OR3A4 and some other long non-coding RNAs participate in this process. In the current review, we describe the role of non-coding RNAs in B cell malignancies.
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http://dx.doi.org/10.1186/s12935-022-02521-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8862212PMC
February 2022

A review on the role of PCA3 lncRNA in carcinogenesis with an especial focus on prostate cancer.

Pathol Res Pract 2022 Mar 11;231:153800. Epub 2022 Feb 11.

Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

The prostate cancer antigen 3 (PCA3) is a long non-coding RNA (lncRNA) with high level of specificity for prostate cancer. This lncRNA has fundamental effects in the prostate carcinogenesis through modulation of expression of miR-132-3p, miR-1261, SREBP1, PRKD3 and LAP2α as well as regulation of p53 signaling. Expression of PCA3 in prostate cancer cells can be enhanced by Snail. Moreover, in vitro studies have documented up-regulation of PCA3 in three other types of neoplastic cells, namely those being originated from choriocarcinoma, ovarian carcinoma and thyroid carcinoma. The diagnostic value of PCA3 in differentiation of prostate cancer from benign prostate hyperplasia has been assessed in different studies. Studies aimed at identification of diagnostic power of PCA3 in prostate cancer using receiver operating characteristic curves have reported area under curve values ranging from 0.66 to 0.86. In the current review, we describe the role of PCA3 in the carcinogenesis particularly in the pathoetiology of prostate cancer. Moreover, we review the results of studies appraising diagnostic value of this lncRNA in prostate cancer.
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http://dx.doi.org/10.1016/j.prp.2022.153800DOI Listing
March 2022

Genome sequence analysis of SARS-COV-2 isolated from a COVID-19 patient in Erbil, Iraq.

Appl Nanosci 2022 Feb 7:1-7. Epub 2022 Feb 7.

Department of Biology, College of Education, Salahaddin University, Kurdistan Region, Iraq.

In the city of Wuhan, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first recognized among humans at the end of December 2019, and has since spread to every country around the world. The emergence of this new coronavirus has attracted global attention to work towards finding a treatment and developing an effective vaccine against the virus. In this study, we sequence a full genome of SARS-COV-2 isolated from a male patient in the city of Erbil, Iraq. The virus was sequenced using Sanger sequencer and 21 distinct mutations were found in our isolate compared to the full genome sequence of the SARS-COV-2 isolated from the city of Wuhan/China (Accession number: NC_045512.2). Sequence analysis showed that four of the mutations were located at the spike glycoprotein (S), and ten of them were in nonstructural proteins (nsp1, nsp3, nsp12, and orf3a), which had been shown to be related to structural changes at various sites. Moreover, phylogenetic analysis and transmission supported the conclusion that the cases in Iraq were of independent origins of infections and had a close relation to the isolates from Iran. This is the first report on the DNA sequence of the SARS-CoV-2 genome isolated from the Kurdistan region of Iraq.
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http://dx.doi.org/10.1007/s13204-021-02300-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8818371PMC
February 2022

Emerging role of non-coding RNAs in the regulation of KRAS.

Cancer Cell Int 2022 Feb 9;22(1):68. Epub 2022 Feb 9.

Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

The Kirsten ras oncogene KRAS is a member of the small GTPase superfamily participating in the RAS/MAPK pathway. A single amino acid substitution in KRAS gene has been shown to activate the encoded protein resulting in cell transformation. This oncogene is involved in the malignant transformation in several tissues. Notably, numerous non-coding RNAs have been found to interact with KRAS protein. Such interaction results in a wide array of human disorders, particularly cancers. Orilnc1, KIMAT1, SLCO4A1-AS1, LINC01420, KRAS1P, YWHAE, PART1, MALAT1, PCAT-1, lncRNA-NUTF2P3-001 and TP53TG1 are long non-coding RNAs (lncRNAs) whose interactions with KRAS have been verified in the context of cancer. miR-143, miR-96, miR-134 and miR-126 have also been shown to interact with KRAS in different tissues. Finally, circITGA7, circ_GLG1, circFNTA and circ-MEMO1 are examples of circular RNAs (circRNAs) that interact with KRAS. In this review, we describe the interaction between KRAS and lncRNAs, miRNAs and circRNAs, particularly in the context of cancer.
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http://dx.doi.org/10.1186/s12935-022-02486-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8827276PMC
February 2022

Oncogenic Roles of Small Nucleolar RNA Host Gene 7 (SNHG7) Long Noncoding RNA in Human Cancers and Potentials.

Front Cell Dev Biol 2021 17;9:809345. Epub 2022 Jan 17.

Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Long noncoding RNAs (lncRNAs) are a class of noncoding transcripts characterized with more than 200 nucleotides of length. Unlike their names, some short open reading frames are recognized for them encoding small proteins. LncRNAs are found to play regulatory roles in essential cellular processes such as cell growth and apoptosis. Therefore, an increasing number of lncRNAs are identified with dysregulation in a wide variety of human cancers. SNHG7 is an lncRNA with upregulation in cancer cells and tissues. It is frequently reported with potency of promoting malignant cell behaviors and . Like oncogenic/tumor suppressor lncRNAs, SNHG7 is found to exert its tumorigenic functions through interaction with other biological substances. These include sponging target miRNAs (various numbers are identified), regulation of several signaling pathways, transcription factors, and effector proteins. Importantly, clinical studies demonstrate association between high SNHG7 expression and clinicopathological features in cancerous patients, worse prognosis, and enhanced chemoresistance. In this review, we summarize recent studies in three eras of cell, animal, and human experiments to bold the prognostic, diagnostic, and therapeutic potentials.
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http://dx.doi.org/10.3389/fcell.2021.809345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8801878PMC
January 2022

Aberrant expression of miRNAs in epilepsy.

Mol Biol Rep 2022 Jan 28. Epub 2022 Jan 28.

Functional Neurosurgery Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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.
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http://dx.doi.org/10.1007/s11033-022-07188-5DOI Listing
January 2022

The Emerging Role of Non-Coding RNAs in the Regulation of Virus Replication and Resultant Cellular Pathologies.

Int J Mol Sci 2022 Jan 13;23(2). Epub 2022 Jan 13.

Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran P.O. Box 14155-6153, Iran.

Non-coding RNAs, particularly lncRNAs and miRNAs, have recently been shown to regulate different steps in viral infections and induction of immune responses against viruses. Expressions of several host and viral lncRNAs have been found to be altered during viral infection. These lncRNAs can exert antiviral function via inhibition of viral infection or stimulation of antiviral immune response. Some other lncRNAs can promote viral replication or suppress antiviral responses. The current review summarizes the interaction between ncRNAs and herpes simplex virus, cytomegalovirus, and Epstein-Barr infections. The data presented in this review helps identify viral-related regulators and proposes novel strategies for the prevention and treatment of viral infection.
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http://dx.doi.org/10.3390/ijms23020815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8775676PMC
January 2022
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