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Book ; Online: Molecular Function and Regulation of Non-coding RNAs in Multifactorial Diseases

Faghihi, Mohammad Ali / Mowla, Seyed Javad / Hajjari, Mohammadreza

2016

Abstract: Our understanding of the mechanisms underlying the development of multifactorial diseases such as diabetes, autism, Alzheimers disease, and cancer has been greatly advanced. Non-coding RNAs (ncRNAs), generally including microRNAs and long non-coding RNAs, ...

Abstract	Our understanding of the mechanisms underlying the development of multifactorial diseases such as diabetes, autism, Alzheimers disease, and cancer has been greatly advanced. Non-coding RNAs (ncRNAs), generally including microRNAs and long non-coding RNAs, have recently been found to have potential roles in these diseases, and provide new opportunities for developing both specific biomarkers and therapeutic targets. However, the molecular function and regulation of these RNAs still remains challenging. Numerous studies are focusing on this field in order to fully appreciate the role and regulation of these molecules in human medicine and biology. This e-book aims to bring together new findings on Non-coding RNAs in different complex diseases. It will highlight the characterization, roles, mechanism, and mode of action of these RNAs in complex disorders. We believe that the publications on this topic would be exponentially extended in future. The improved approaches at multiple levels may pave the way for designing and applying new biomarker and therapeutic targets for specific diseases based on these attractive molecules
Keywords	Genetics ; Science (General)
Size	1 electronic resource (71 p.)
Publisher	Frontiers Media SA
Document type	Book ; Online
Note	English ; Open Access
HBZ-ID	HT020094967
ISBN	9782889450022 ; 2889450023
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: Novel splice variants of LINC00963 suppress colorectal cancer cell proliferation via miR-10a/miR-143/miR-217/miR-512-mediated regulation of PI3K/AKT and Wnt/β-catenin signaling pathways.

Ghaemi, Zahra / Mowla, Seyed Javad / Soltani, Bahram Mohammad

Biochimica et biophysica acta. Gene regulatory mechanisms

2023 Volume 1866, Issue 2, Page(s) 194921

Abstract: Emerging evidence has shown lncRNAs play important roles in signaling pathways involved in colorectal cancer (CRC) carcinogenesis. However, only a few functional lncRNAs have been extensively researched, especially in CRC-related signaling pathways. ... ...

Abstract	Emerging evidence has shown lncRNAs play important roles in signaling pathways involved in colorectal cancer (CRC) carcinogenesis. However, only a few functional lncRNAs have been extensively researched, especially in CRC-related signaling pathways. Looking for novel candidate regulators of CRC incidence and progression, using available RNA-seq and microarray datasets, LINC00963 was introduced as a bona fide oncogenic-lncRNA. Consistently, RT-qPCR results showed that LINC00963 was up-regulated in CRC tissues. However, our attempt to amplify the full-length lncRNA from cDNA resulted in the discovery of two novel variants (LINC00963-v2 & LINC00963-v3) that surprisingly, were downregulated in CRC tissues, detected by RT-qPCR. Overexpression of LINC00963-v2/-v3 in HCT116 and SW480 cells resulted in downregulation of the major oncogenes and upregulation of the main tumor suppressor genes involved in PI3K and Wnt signaling, verified through RT-qPCR, western blotting, and TOPFlash assays. Mechanistic studies revealed that LINC00963-v2/-v3 exert their effect on PI3K and Wnt signaling through sponging miR-10a-5p, miR-143-3p, miR-217, and miR-512-3p, which in turn these miRNAs are fine-regulators of PTEN, APC1, and Axin1 tumor suppressor genes verified by dual-luciferase assay and RT-qPCR. At cellular levels, LINC00963-v2/-v3 overexpression suppressed cell proliferation, viability, and migration while increasing the apoptosis of CRC cell lines, detected by PI flow cytometry, colony formation, MTT, RT-qPCR, wound-healing, Transwell, AnnexinV-PE/7AAD, caspase3/7 activity assays, and Hoechst/PI-AO/EB staining. Overall, our results indicate that LINC00963-v2 & -v3 are novel tumor suppressor ceRNAs that attenuate the PI3K and Wnt pathways during CRC incidence and these lncRNAs may serve as potential targets for CRC therapy.
MeSH term(s)	Humans ; Wnt Signaling Pathway/genetics ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism ; Proto-Oncogene Proteins c-akt/genetics ; Proto-Oncogene Proteins c-akt/metabolism ; Phosphatidylinositol 3-Kinases/genetics ; Phosphatidylinositol 3-Kinases/metabolism ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/metabolism ; Colorectal Neoplasms/pathology ; Cell Line, Tumor ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Cell Proliferation/genetics
Chemical Substances	RNA, Long Noncoding ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; MicroRNAs ; MIRN143 microRNA, human ; MIRN217 microRNA, human ; MIRN512 microRNA, human
Language	English
Publishing date	2023-02-17
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2918786-2
ISSN	1876-4320 ; 1874-9399
ISSN (online)	1876-4320
ISSN	1874-9399
DOI	10.1016/j.bbagrm.2023.194921
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Article ; Online: ErbB4-encoded novel miRNAs act as tumor suppressors by regulating ErbB/PI3K signaling.

Ghaemi, Zahra / Soltani, Bahram M / Mowla, Seyed Javad

Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine

2022 Volume 44, Issue 1, Page(s) 215–230

Abstract: Background: ErbB/PI3K signaling is widely recognized as a critical modulator of malignancy and miRNAs have been found to play a crucial role in the regulation of this pathway.: Objective: This study aimed to identify novel miRNAs related to the ErbBs ...

Abstract	Background: ErbB/PI3K signaling is widely recognized as a critical modulator of malignancy and miRNAs have been found to play a crucial role in the regulation of this pathway. Objective: This study aimed to identify novel miRNAs related to the ErbBs loci and investigate the functional effects of these miRNAs on ErbB/PI3K signaling in cancer progression. Materials and methods: Bioinformatics tools and RNA-seq data were used to discover novel miRNAs in breast and colon cancer cells. Gene expression levels were determined using RT-qPCR. Western blotting and dual-luciferase assays were used to identify the regulatory mechanism between ErbB4-miR1/2 and related genes. The effects of ErbB4-miR1/2 on cell proliferation, viability, ROS production, and migration were assessed by PI-flow cytometry, colony formation, MTT, ROS, scratch, and transwell assays in SKBR3 and SW480 cells. Results: MicroRNA prediction tools, RNA-seq data, RT-qPCR, and sequencing results identified ErbB4-miR1 and ErbB4-miR2 (ErbB4-miR1/2) as novel miRNAs encoded by ErbB4 gene. ErbB4-miR1/2 were downregulated in breast and colon tumor tissues and also in different cancerous cells. RT-qPCR and dual-luciferase assays revealed that ErbB2 and ErbB3 genes are regulated by ErbB4-miR1/2. Consistently, a decrease in the p-AKT/AKT protein ratio verified the suppressive effect of ErbB4-miR1/2 on ErbB/PI3K activity. Furthermore, ErbB4-miR1/2 overexpression suppressed cell proliferation, viability, and migration, and increased ROS production. Conclusions: ErbB4-miR1/2 are novel tumor suppressor miRNAs which attenuate ErbB/PI3K signaling in breast and colon cancer cells.
MeSH term(s)	Humans ; MicroRNAs/genetics ; Phosphatidylinositol 3-Kinases/genetics ; Proto-Oncogene Proteins c-akt ; Reactive Oxygen Species ; Receptor, ErbB-4/genetics ; Colonic Neoplasms/genetics
Chemical Substances	MicroRNAs ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Reactive Oxygen Species ; Receptor, ErbB-4 (EC 2.7.10.1) ; ERBB4 protein, human (EC 2.7.10.1)
Language	English
Publishing date	2022-11-28
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	605825-5
ISSN	1423-0380 ; 0289-5447 ; 1010-4283
ISSN (online)	1423-0380
ISSN	0289-5447 ; 1010-4283
DOI	10.3233/TUB-211570
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Article: MicroRNAs associated with signaling pathways and exercise adaptation in sarcopenia

Javanmardifard, Zahra / Shahrbanian, Shahnaz / Mowla, Seyed Javad

Life sciences. 2021 Nov. 15, v. 285

2021

Abstract: Considering the expansion of human life-span over the past few decades; sarcopenia, a physiological consequence of aging process characterized with a diminution in mass and strength of skeletal muscle, has become more frequent. Thus, there is a growing ... ...

Abstract	Considering the expansion of human life-span over the past few decades; sarcopenia, a physiological consequence of aging process characterized with a diminution in mass and strength of skeletal muscle, has become more frequent. Thus, there is a growing need for expanding our knowledge on the molecular mechanisms of muscle atrophy in sarcopenia which are complex and involve many signaling pathways associated with protein degradation and synthesis. MicroRNAs (miRNAs) as evolutionary conserved small RNAs, could complementarily bind to their target mRNAs and post-transcriptionally inhibit their translation. Aberrant expression of miRNAs contributes to the development of sarcopenia by regulating the expression of critical genes involved in age-related skeletal muscle mass loss. Here we have a review on the signaling pathways along with the miRNAs controlling their components expression and subsequently we provide a brief overview on the effects of exercise on expression pattern of miRNAs in sarcopenia.
Keywords	exercise ; humans ; microRNA ; protein degradation ; sarcopenia ; skeletal muscle
Language	English
Dates of publication	2021-1115
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2021.119926
Database	NAL-Catalogue (AGRICOLA)

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Article: Post-Transcriptional Effects of miRNAs on PCSK7 Expression and Function: miR-125a-5p, miR-143-3p, and miR-409-3p as Negative Regulators.

Malakootian, Mahshid / Naeli, Parisa / Mowla, Seyed Javad / Seidah, Nabil G

Metabolites

2022 Volume 12, Issue 7

Abstract: The regulatory mechanism ... ...

Abstract	The regulatory mechanism of
Language	English
Publishing date	2022-06-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662251-8
ISSN	2218-1989
ISSN	2218-1989
DOI	10.3390/metabo12070588
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Article ; Online: A Novel miRNA Located in the

Shabaninejad, Zahra / Mowla, Seyed Javad / Yousefi, Fatemeh / Soltani, Bahram Mohammad

BioMed research international

2022 Volume 2022, Page(s) 7216758

Abstract: Human epidermal growth factor receptor 2 (HER2) is involved in the development of the majority of cancers. Therefore, it can be a potential target for cancer therapy. It was hypothesized that some of the broad effects ... ...

Abstract	Human epidermal growth factor receptor 2 (HER2) is involved in the development of the majority of cancers. Therefore, it can be a potential target for cancer therapy. It was hypothesized that some of the broad effects of
MeSH term(s)	Cell Cycle/genetics ; Cell Division ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Genes, erbB-2 ; HEK293 Cells ; HeLa Cells ; Humans ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Wnt Signaling Pathway/genetics
Chemical Substances	MicroRNAs
Language	English
Publishing date	2022-06-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	2698540-8
ISSN	2314-6141 ; 2314-6133
ISSN (online)	2314-6141
ISSN	2314-6133
DOI	10.1155/2022/7216758
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Article: MicroRNA and Hemophilia-A Disease: Bioinformatics Prediction and Experimental Analysis.

Rezaei, Halimeh / Motovali-Bashi, Majid / Mowla, Seyed Javad

Cell journal

2021 Volume 23, Issue 3, Page(s) 341–348

Abstract: Objective: Hemophilia-A is a common genetic abnormality resulted from decreased or lack of factor VIII (FVIII) pro-coagulant protein function caused by mutations in the : Materials and methods: In this experimental study, bioinformatics tools have ... ...

Abstract	Objective: Hemophilia-A is a common genetic abnormality resulted from decreased or lack of factor VIII (FVIII) pro-coagulant protein function caused by mutations in the Materials and methods: In this experimental study, bioinformatics tools have been utilized to seek the novel microRNAs inserted within human Results: We are unable to confirm existence of the considered mature microRNAs in the transfected cells. Conclusion: We hope that through changing experimental conditions, designing new primers or altering cell lines as well as the expression of vectors, exogenous and endogenous expressions of the predicted miRNA will be confirmed.
Language	English
Publishing date	2021-07-17
Publishing country	Iran
Document type	Journal Article
ZDB-ID	2647430-X
ISSN	2228-5814 ; 2228-5806
ISSN (online)	2228-5814
ISSN	2228-5806
DOI	10.22074/cellj.2021.7109
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Article: Synthetic miR-21 decoy circularized by tRNA splicing mechanism inhibited tumorigenesis in glioblastoma

Bayat, Hadi / Pourgholami, Mohammad Hossein / Rahmani, Saeid / Pournajaf, Safura / Mowla, Seyed Javad

Molecular therapy. Nucleic acids

2023 Volume 32, Page(s) 432–444

Abstract: Glioblastoma multiforme (GBM) is the deadliest primary central nervous system tumor. miRNAs (miRs), a class of non-coding RNAs, are considered pivotal post-transcriptional regulators of cell signaling pathways. miR-21 is a reliable oncogene that promotes ...

Abstract	Glioblastoma multiforme (GBM) is the deadliest primary central nervous system tumor. miRNAs (miRs), a class of non-coding RNAs, are considered pivotal post-transcriptional regulators of cell signaling pathways. miR-21 is a reliable oncogene that promotes tumorigenesis of cancer cells. We first performed an
Language	English
Publishing date	2023-04-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2662631-7
ISSN	2162-2531
ISSN	2162-2531
DOI	10.1016/j.omtn.2023.04.001
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Article ; Online: Functional analysis of a putative HER2-associated expressed enhancer, Her2-Enhancer1, in breast cancer cells.

Rojhannezhad, Mahdieh / Soltani, Bahram M / Vasei, Mohammad / Ghorbanmehr, Nassim / Mowla, Seyed Javad

Scientific reports

2023 Volume 13, Issue 1, Page(s) 19516

Abstract: HER-2/neu (HER2) is a member of the epidermal growth factor receptors family, encoding a protein with tyrosine kinase activity. Following the gene amplification or increased HER2 transcription, carcinogenesis has been observed in some cancers. Genetic ... ...

Abstract	HER-2/neu (HER2) is a member of the epidermal growth factor receptors family, encoding a protein with tyrosine kinase activity. Following the gene amplification or increased HER2 transcription, carcinogenesis has been observed in some cancers. Genetic and epigenetic changes occurring in enhancer sequences can deeply affect the expression and transcriptional regulation of downstream genes, which can cause some physiological and pathological changes, including tumor progression. A therapeutic approach that directly targets the genomic sequence alterations is of high importance, with low side effects on healthy cells. Here, we employed the CRISPR/Cas9 method to genetically knockout an expressed putative enhancer (GH17J039694; we coined it as Her2-Enhancer1) located within the HER2 gene, 17q12: 39,694,339-39,697,219 (UCSC-hg38). We then investigated the potential regulatory effect of Her2-Enhancer1 on HER2 and HER2-interacting genes. To evaluate the cis and trans effects of Her2-Enhancer1, genetic manipulation of this region was performed in HER2-positive and -negative breast cancer cells. Our bioinformatics and real-time PCR data revealed that this putative enhancer region is indeed expressed, and acts as an expressed enhancer. Further functional analysis on edited and unedited cells revealed a significant alteration in the expression of HER2 variants, as well as some other target genes of HER2. Moreover, the apoptosis rate was considerably elevated within the edited cells. As we expected, Western blot analysis confirmed a reduction in protein levels of HER2, GRB7, the gene interacting with HER2, and P-AKT in the PI3K/AKT pathway. Altogether, our findings revealed an enhancer regulatory role for Her2-Enhancer1 on HER2 and HER2-interacting genes; and that this region has a potential for targeted therapy of HER2-positive cancers.
MeSH term(s)	Proto-Oncogene Proteins c-akt/genetics ; Proto-Oncogene Proteins c-akt/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Oncogenes ; Phosphorylation ; Blotting, Western ; Neoplasms/genetics
Chemical Substances	Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-)
Language	English
Publishing date	2023-11-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-46460-x
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Article ; Online: Associations between low serum levels of ANRIL and some common gene SNPs in Iranian patients with premature coronary artery disease.

Taheri Bajgan, Elham / Zahedmehr, Ali / Shakerian, Farshad / Maleki, Majid / Bakhshandeh, Hooman / Mowla, Seyed Javad / Malakootian, Mahshid

Scientific reports

2024 Volume 14, Issue 1, Page(s) 1244

Abstract: Coronary artery disease (CAD) is the major cause of mortality in the world. Premature development of CAD can be attributed to women under 55 and men under 45. Many genetic factors play a part in premature CAD. Among them, ANRIL, a long noncoding RNA is ... ...

Abstract	Coronary artery disease (CAD) is the major cause of mortality in the world. Premature development of CAD can be attributed to women under 55 and men under 45. Many genetic factors play a part in premature CAD. Among them, ANRIL, a long noncoding RNA is located at the 9p21 risk locus, and its expression seems to be correlated with CAD. In the current study, premature CAD and control blood samples, with and without Type 2 Diabetes (T2D), were genotyped for six SNPs at the 9p21 locus. Additionally, ANRIL serum expression was assessed in both groups using real-time PCR. It was performed using different primers targeting exons 1, 5-6, and 19. The χ
MeSH term(s)	Female ; Humans ; Male ; Coronary Artery Disease/genetics ; Diabetes Mellitus, Type 2/genetics ; Genetic Predisposition to Disease ; Iran ; Polymorphism, Single Nucleotide ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism
Chemical Substances	RNA, Long Noncoding ; CDKN2B antisense RNA, human
Language	English
Publishing date	2024-01-13
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-51715-2
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