Articles
Behrouzi abady pamsary, S.,
Esmaeili, F.,
Dehghanian, F.,
Bahadori, M.H. Human Molecular Genetics (14602083)34(7)pp. 599-610
Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder characterized by the progressive loss of nigrostriatal dopaminergic neurons (DA) which can be caused by environmental and genetic factors. lncRNAs have emerged as an important regulatory layer in neurodegenerative disorders, including PD. In this study, we investigated and validated lncRNAs that may serve as diagnostic or therapeutic targets for PD. Key genes associated with midbrain and DA cells were screened by differential gene expression analysis on GSE213100 dataset and candidate lncRNAs were selected for further examination. P19 cells were differentiated into DA cells and received treatment with MPP+ to induce PD-like cytotoxic events, which were confirmed by light microscopy, RT-qPCR, immunofluorescence and flow cytometry. Then, the cells were used to investigate the changes of lncRNAs Malat1, Norad, Snhg1 and Meg3. Here we found that the neuronal phenotype was mainly observed on the 12th day of differentiation and the number of DA markers significantly decreased in PD model cells compared with the control group. Moreover, the expression levels of Meg3, Norad, and Snhg1 were decreased by MPP+ whereas Malat1 level was noticeably higher in MPP+ cells compared to DA cells and the control group. In conclusion, the expression level of lncRNAs was able to show a significant difference between differentiated dopaminergic cells and their Parkinsonian model, thereby improving our understanding of the molecular pathogenesis of PD. © The Author(s) 2025. Published by Oxford University Press. All rights reserved.
Ahmadi beni, F.,
Abdolvand, M.,
Poorbafrani, F.,
Salehi, M.,
Dehghanian, F.,
Kazemi, M. Egyptian Journal of Medical Human Genetics (11108630)26(1)
Background: Colorectal cancer (CRC) is the third most frequent cancer and the second deadliest cancer, worldwide. Long noncoding RNAs (lncRNAs) have been introduced as crucial regulators of CRC. lncRNA feline leukemia virus subgroup C receptor 1 antisense RNA 1 (FLVCR1‑AS1) is suggested to play a significant role in the tumorigenesis of several cancers. The Wnt signaling pathway is the most deregulated pathway in CRC. Objective: The present study aimed to investigate the underlying mechanism of function of FLVCR1-AS1 in CRC through FLVCR1-AS1/miR-381-3p/CTNNB1, LRP6, and FZD3 axis. Methods: The expression levels of FLVCR1-AS1 were analyzed in colorectal cancer (CRC) tissues compared to adjacent normal tissues, as well as across various CRC cell lines. In HCT116 cells, FLVCR1-AS1 was knocked down, and the subsequent effects on the expression levels of FLVCR1-AS1, miR-381-3p, and three genes were measured using real-time PCR. Proliferation differences were assessed through an MTT assay, while cell death was evaluated using flow cytometry. Results: The results confirmed that FLVCR1-AS1 was upregulated in CRC tissues compared to adjacent normal tissues. RT-qPCR validated that FLVCR1-AS1 has the most level of expression in HT29, HCT116, SW480, and Caco2; respectively. Knockdown of FLVCR1‑AS1 was significantly followed by attenuated viability of HCT116 cells; while resulted in enhancement of apoptosis and necrosis. Conclusion: These findings support the idea that FLVCR1-AS1 may act as an oncogene in CRC, and targeting FLVCR1-AS1/miR-381-3p/CTNNB1, LRP6, and FZD3 axis may be introduced as a novel target for CRC therapy and diagnosis in the future. © The Author(s) 2025.
Dehghanian, F.,
Ghahnavieh, L.E.,
Nilchi, A.N.,
Khalilian, S.,
Joonbakhsh, R. Gene (03781119)916
The most significant factors that lead to cancer-related death in breast cancer (BC) patients include drug resistance, migration, invasion, and metastasis. Several signaling pathways are involved in the development of BC. The different types of BC are initially sensitive to chemotherapy, and drug resistance can occur through multiple molecular mechanisms. Regardless of developing targeted Therapy, due to the heterogenic nature and complexity of drug resistance, it is a major clinical challenge with the low survival rate in BC patients. The deregulation of several signaling pathways, particularly the Hippo pathway (HP), is one of the most recent findings about the molecular mechanisms of drug resistance in BC, which are summarized in this review. Given that HP is one of the recent cancer research hotspots, this review focuses on its implication in BC drug resistance. Unraveling the different molecular basis of HP through its crosstalk with other signaling pathways, and determining the effectiveness of HP inhibitors can provide new insights into possible therapeutic strategies for overcoming chemoresistance in BC. © 2024 Elsevier B.V.
IEEE Transactions on Biomedical Circuits and Systems (19324545)18(3)pp. 478-497
In the last few decades, DNA-based self-assembly tiles has become a hot field in research due to its special applications and advantages. The regularity and strong design methods comprise other DNA-based digital circuit design methods. In addition to the obvious advantages of this method, there are challenges in performing computations based on self-assembly tiles, which have hindered the development and construction of large computing circuits with this method. The first challenge is the creation of crystals from DNA molecules in the output, which has led to the impossibility of cascading. The second challenge of this method is the uncontrollability of the reactions of the tiles, which increases the percentage of computing errors. In this article, these two challenges have been solved by changing the structure of leading tiles so that without the activator strand, tiles remain inactive and cannot be connected to other tiles. Also, when the tiles are activated, single-strand DNA will be released after connecting to other tiles, which will be used as the output of the circuit. This output gives the possibility of cascading to self-assembly designed circuits. The method introduced in this article can be a beginning for the re-development of DNA-based circuit design with the self-assembly tile method. © 2007-2012 IEEE.
Dehghanian, F.,
Bovio, P.P.,
Gather, F.,
Probst, S.,
Naghsh-nilchi, A.,
Vogel, T. Biochimica et Biophysica Acta - Molecular Cell Research (01674889)1871(4)
Background: Understanding the genetic underpinnings of protein networks conferring stemness is of broad interest for basic and translational research. Methods: We used multi-omics analyses to identify and characterize stemness genes, and focused on the zinc finger protein 982 (Zfp982) that regulates stemness through the expression of Nanog, Zfp42, and Dppa3 in mouse embryonic stem cells (mESC). Results: Zfp982 was expressed in stem cells, and bound to chromatin through a GCAGAGKC motif, for example near the stemness genes Nanog, Zfp42, and Dppa3. Nanog and Zfp42 were direct targets of ZFP982 that decreased in expression upon knockdown and increased upon overexpression of Zfp982. We show that ZFP982 expression strongly correlated with stem cell characteristics, both on the transcriptional and morphological levels. Zfp982 expression decreased with progressive differentiation into ecto-, endo- and mesodermal cell lineages, and knockdown of Zfp982 correlated with morphological and transcriptional features of differentiated cells. Zfp982 showed transcriptional overlap with members of the Hippo signaling pathway, one of which was Yap1, the major co-activator of Hippo signaling. Despite the observation that ZFP982 and YAP1 interacted and localized predominantly to the cytoplasm upon differentiation, the localization of YAP1 was not influenced by ZFP982 localization. Conclusions: Together, our study identified ZFP982 as a transcriptional regulator of early stemness genes, and since ZFP982 is under the control of the Hippo pathway, underscored the importance of the context-dependent Hippo signals for stem cell characteristics. © 2024 The Authors
