SMARCAL1, the annealing helicase and the transcriptional co-regulator.

The ATP-dependent chromatin remodeling proteins play an important role in DNA repair. The energy released by ATP hydrolysis is used for myriad functions ranging from nucleosome repositioning and nucleosome eviction to histone variant exchange. In addition, the distant member of the family, SMARCAL1, uses the energy to reanneal stalled replication forks in response to DNA damage. Biophysical studies have shown that this protein has the unique ability to recognize and bind specifically to DNA structures possessing double-strand to single-strand transition regions. Mutations in SMARCAL1 have been linked to Schimke immuno-osseous dysplasia, an autosomal recessive disorder that exhibits variable penetrance and expressivity. It has long been hypothesized that the variable expressivity and pleiotropic phenotypes observed in the patients might be due to the ability of SMARCAL1 to co-regulate the expression of a subset of genes within the genome. Recently, the role of SMARCAL1 in regulating transcription has been delineated. In this review, we discuss the biophysical and functional properties of the protein that help it to transcriptionally co-regulate DNA damage response as well as to bind to the stalled replication fork and stabilize it, thus ensuring genomic stability. We also discuss the role of SMARCAL1 in cancer and the possibility of using this protein as a chemotherapeutic target.

Identification and differential expression of serotransferrin and apolipoprotein A-I in the plasma of HIV-1 patients treated with first-line antiretroviral therapy.

BACKGROUND: Plasma proteins are known to interfere the drug metabolism during therapy. As limited information is available regarding the role of plasma proteins in HIV drug resistance during ART in HIV/AIDS patients, the present study aimed to identify and characterize the differentially expressed plasma proteins in the drug resistant and drug respondent groups of HIV-1 infected patients with > 6 years of first line ART. METHODS: Four-drug resistant (treatment failure) and four-drug respondent (treatment responder) patients were selected for plasma proteomic analysis based on viral load and drug resistance associated mutations from a cohort study designed on the first line ART patients who were enrolled in the antiretroviral therapy center, Sarojini Naidu Medical College, Agra, India from December 2009 to November 2016. After depleting high abundant proteins, plasma proteins were resolved using two-dimensional gel electrophoresis on IPG strips, pH range of 3-10. Spots were selected in the gel based on the density of staining which was common in the drug resistant and drug respondent groups separately. The fold change of each spot was calculated using image-J. Each protein spot was identified using the matrix assisted laser desorption/ionization-time of flight/time of flight (MALDI-TOF/TOF) after tryptic digestion. Peptide peaks were identified through flex analysis version 3.3, and a search against a protein data base using the internal Mascot. Gene ontology study was completed through STRING v.11 and Panther15.0. RESULTS: Out of eight spots from 2D gel samples analyzed by MALDITOF/TOF, two proteins were found to have significant score (> 56) after Flex analysis. These two proteins were identified to be apolipoprotein A1 and serotransferrin. The fold change expression of these two proteins were analyzed in drug resistant and drug respondent group. Apolipoprotein-A1 and serotransferrin were observed to be expressed 1.76 and 1.13-fold more respectively in drug respondent group compared to drug resistant group. The gene ontology analysis revealed the involvement of these two proteins in various important physiological processes. CONCLUSION: Apolipoprotein A-I and serotransferrin were found to be expressed more in drug respondent group compared to drug resistant group.

Recent insights into Mycobacterium tuberculosis through proteomics and implications for the clinic.

INTRODUCTION: This review aimed at providing an update on the application of proteomics-based approaches to gain recent insights of Mycobacterium tuberculosis (M.tb) and its relevance to clinic. Proteomics and bioinformatics approaches helped in the identification and characterization of novel proteins. Studying M.tb, causative agent of tuberculosis (TB), at the proteomic level can contribute to the identification of proteins which can be considered as potential targets for developed drugs and can help us in better understanding the pathogen physiology. Areas covered: In this review we have presented a comprehensive literature pertaining to role of proteomics in understanding M.tb. We have also focused on how the development and advancement in technology in the field of proteomics has augmented the research and played a pivotal role in answering many unexplored questions. Lastly, the application of proteomics to clinic has also been discussed. Expert commentary: We envisage that proteomics has gained remarkable momentum over the years. Proteomics can play an important role in the discovery of biomarkers for TB and other diseases. Also, it can aid in development of effective vaccines and simple, rapid and cost-effective test for the diagnosis of TB which is crucial for the management and control of the disease.

Identification of factors involved in Enterococcus faecalis biofilm under quercetin stress.

Enterococcus faecalis is a gram positive enteric commensal bacteria or opportunistic pathogen and its infection involves biofilm formation. Quercetin, a plant origin polyphenol was found to inhibit E. faecalis biofilm. Crystal violet assay, SEM and CLSM microscopy confirmed biofilm inhibition by quercetin. Proteomics was used to elucidate the changes occurred in bacterial cell by quercetin treatment. 2D-Electrophorosis and MALDI-TOF analysis revealed that nineteen proteins were differentially expressed in quercetin treated sample. Glycolytic pathways, protein translation-elongation pathways and protein folding pathways were under differential expression after treatment. Real Time-PCR (RT-PCR) validated the proteomic data at genomic level except for the translation elongation factor G which showed opposite data to proteomics. Protein-protein interaction networks constructed using STRING 10.0 demonstrated strong connection of translation-elongation proteins with many important proteins. The results of the comparative analysis indicate that quercetin exerts its inhibitory effect by disturbing glycolytic, protein translation-elongation and protein folding pathways. This disturbs bacterial physiology and stops transition of planktonic cells to biofilm state.

Role of M.tuberculosis protein Rv2005c in the aminoglycosides resistance.

Tuberculosis is an airborne infectious disease caused by Mycobacterium tuberculosis which threatens the globe. Aminoglycosides {Amikacin (AK) & Kanamycin (KM)} are WHO recommended second-line anti-TB drugs used against the treatment of drug-resistant tuberculosis. Aminoglycosides target the steps of protein translation machinery of M.tuberculosis. Several mechanisms have been put forward to elucidate the phenomena of aminoglycosides resistance but our knowledge is still insufficient. The aim of the study was to understand the involvement of Mycobacterium tuberculosis universal stress protein (Rv2005c) in aminoglycosides resistance and virulence. To establish the relationship of universal stress protein Rv2005c with AK & KM resistance, Rv2005c was cloned, expressed in E.coli BL21 using pQE2 expression vector and antimicrobial drug susceptibility testing (DST) was carried out. STRING-10 was also used to predict the interacting protein partners of Rv2005c. DST showed that the minimum inhibitory concentration of induced recombinant cells (Rv2005c) were five and four folds shifted with AK and KM E-strips, respectively. STRING-10 showed the interacting protein partners of Rv2005c. Overexpression of Rv2005c leads to shifting in MIC which might be signifying its involvement in the survival/resistance of Mycobacteria by inhibiting/modulating the effects of AK and KM released from the E-strips. Interactome also suggests that Rv2005c and its interacting protein partners are cumulatively involved in M.tuberculosis resistance, stresses, and latency.

Prevalence and risk factors of tuberculosis in developing countries through health care workers.

In the last two decades, tuberculosis (TB) have threatened the public across the globe and continuing new TB cases and their transmission pooled with the global emergence of drug-resistant strains present an enduring occupational risk for health care workers (HCWs). Since last decade, government and funding agencies has given a significant amount of funds to tackle the problem of TB infection among medical staff or HCW in hospitals of developing countries, but the effects of these efforts have not yet been reported. Working environments are the major risk factors for TB infections among the HCW in hospital settings. Twenty-two high burden countries endorsed to the preponderance of worldwide tuberculosis cases in 2015. Urgent preventive strategies and mediations are needed to ensure the safety and sustained availability of these exquisite healthcare resources. This timeline review will provide the theoretical basis of high TB burden among the HCW which can be used for further improvement in strategies for the prevention of TB infections in hospital settings and provide a reliable basis for improving the personal health of HCW or medical staff.

Interactome analysis of Rv0148 to predict potential targets and their pathways linked to aminoglycosides drug resistance: An insilico approach.

Failure of multi drug resistant tuberculosis (MDR-TB) treatment has increased the risk of aminoglycosides resistance, disease transmission, morbidity and mortality. Aminoglycosides are commonly used in multi drug resistant tuberculosis (MDR-TB) treatment. They inhibit protein synthesis by interacting with translationary steps. Apart from gene mutations various mechanisms of aminoglycosides resistance have been reported but still our knowledge regarding aminoglycosides resistance is fragmentary. Proteomics and bioinformatics approaches are the most accepted approaches to explore the unrevealed mechanisms of aminoglycosides resistance. Our previous studies suggested that over expression of Rv0148 in aminoglycosides resistant M. tuberculosis clinical isolates potentially leads to aminoglycosides resistance. In this study we have analyzed the protein-protein interactions of putative short-chain type dehydrogenase/reductase (Rv0148) and predicted the proteins target linked to the aminoglycosides drug resistance. Interactome predicted that fatty acid synthase (fas), dehydrogenase (htdY), dehydrogenase (MT3642), quinine oxidoreductase (MT0157), phenyloxazoline synthase (mbtB), hypothetical protein (Rv0130), 3-oxoacyl-ACP synthase (kasA), 3-oxoacyl-ACP synthase (kasB) aldehyde dehydrogenase (MT0155) and hypothetical protein (Rv1867) were the interactive partners of Rv0148. We have suggested that Rv0148, its predictive interactive protein partners and their pathways (via lipid metabolism as well as intermediary metabolism and respiration) cumulatively unlock the mystery of aminoglycosides resistance in M. tuberculosis.

Characterization of FtsY, its interaction with Ffh, and proteomic identification of their potential substrates in Mycobacterium tuberculosis.

The universally conserved signal recognition particle (SRP) pathway that mediates co-translational targeting of membrane and secretory proteins is essential for eukaryotic and prokaryotic cells. The Mycobacterium tuberculosis SRP pathway consists of 2 proteins, Ffh and FtsY, and a 4.5S RNA molecule. Although the Escherichia coli SRP pathway is well studied, understanding of the M. tuberculosis SRP pathway components is very limited. In this study, we have overexpressed and characterized the M. tuberculosis SRP receptor (SR) FtsY as a GTP binding protein. Further, we established the direct protein-protein interaction between Ffh and FtsY. The Ffh-FtsY complex formation resulted in mutual stimulation of their GTP hydrolysis activity. We also attempted to biochemically characterize the SRP components by constructing the antisense gene knockdown strains of ffh and ftsY in M. tuberculosis. Loss of ffh and ftsY resulted in a decreased in vitro growth rate of the antisense ffh strain as compared with the antisense ftsY strain. Finally, 2-D gel electrophoresis of antisense depleted ffh and ftsY strains identified differential expression of 14 proteins.

Plants in our combating strategies against Mycobacterium tuberculosis: progress made and obstacles met.

CONTEXT: Traditionally used plants for treating chest-related problems/tuberculosis (TB) have not been evaluated in detail and hence a thorough study is needed in this regard. This knowledge may find application in developing new anti-TB drugs. OBJECTIVE: This article elaborates on studying the activity of medicinal plants against different forms of Mycobacterium tuberculosis (Mtb) using different model strains, in vitro and ex vivo assays for studying the tuberculocidal activity and discusses the results from different studies on the activity against different forms of Mtb and human immunodeficiency virus-tuberculosis (HIV-TB) co-infection. METHODS: Scientific databases such as PubMed, Elsevier, Scopus, Google scholar, were used to retrieve the information from 86 research articles (published from 1994 to 2016) related to the topic of this review. RESULTS: Twenty-three plant species have been reported to possess active molecules against multi-drug resistant (MDR) isolates of Mtb. Seven plants were found to be active against intracellular Mtb and six against dormant bacilli. Seven plants were synergistically effective when combined with anti-TB drugs. Six studies suggest that the beneficial effects of plant extracts are due to their wide array of immuno-modulatory effects manifested by the higher expression of cytokines. Some studies have also shown the dual activity (anti-HIV and anti-TB) of plants. CONCLUSION: We emphasize on identifying plants based on traditional uses and testing their extracts/phytomolecules against MDR strains, intracellular Mtb as well as against dormant Mtb. This will help in future to shorten the current therapeutic regimens for TB and also for treating HIV-TB co-infection.

Protein translation machinery holds a key for transition of planktonic cells to biofilm state in Enterococcus faecalis: A proteomic approach.

Enterococcus faecalis is a member of human gut microflora causing nosocomial infection involving biofilm formation. Ethyl methyl sulfonate induced mutants were analysed using crystal violet assay, SEM and CLSM microscopy which confirmed AK-E12 as biofilm efficient and AK-F6 as biofilm deficient mutants. Growth curve pattern revealed AK-E12 was fast growing whereas, AK-F6 was found slow growing mutant. 2D-Electrophorosis and MALDI-TOF analysis revealed over and underexpression of many translation-elongation associated proteins in mutants compared to wild type. Protein translation elongation factor G, translation elongation factor Tu and ribosomal subunit interface proteins were underexpressed and UTP-glucose-1-phosphate uridylyl transferase and cell division protein divIVA were overexpressed in AK-E12 as compared to wild type. In AK-F6, except 10 kDa chaperonin which was over-expressed other selected proteins were found to be suppressed. RT-PCR confirmed proteomic data except for the translation elongation factor G which showed contradictory data of proteome expression in AK-E12. Protein-protein interaction networks were constructed using STRING 10.0 which demonstrated strong connection of translation-elongation proteins with other proteins. Hence, it concludes from the data that translation elongation factors are important in transition of planktonic cells to biofilm cells in Enterococcus faecalis.

M. tuberculosis ferritin (Rv3841): Potential involvement in Amikacin (AK) & Kanamycin (KM) resistance.

Tuberculosis is an infectious disease, caused by one of the most successful human pathogen, Mycobacterium tuberculosis. Aminoglycosides, Amikacin (AK) & Kanamycin (KM) are commonly used to treat drug resistant tuberculosis. They target the protein synthesis machinery by interacting with several steps of translation. Several explanations have been proposed to explain the mechanism of aminoglycoside resistance but still our information is inadequate. Iron storing/interacting proteins were found to be overexpressed in aminoglycosides resistant isolates. Iron assimilation and utilization in M. tuberculosis plays a crucial role in growth, virulence and latency. To establish the relationship of ferritin with AK & KM resistance ferritin (Rv3841/bfrB) was cloned, expressed and antimicrobial drug susceptibility testing (DST) was carried out. Rv3841/bfrB gene was cloned and expressed in E. coli BL21 using pQE2 expression vector. Etest results for DST against AK & KM showed that the minimum inhibitory concentration (MIC) of ferritin recombinant cells was changed. Recombinants showed two fold changes in MIC with AK and three fold with KM E-strips. Overexpression of ferritin reflect the MIC shift which might be playing a critical role in the survival of mycobacteria by inhibiting/modulating the effects of AK & KM. String analysis also suggests that ferritin interacted with few proteins which are directly and indirectly involved in M. tuberculosis growth, Iron assimilation, virulence, resistance, stresses and latency.

An efficient and rapid method for enrichment of lipophilic proteins from Mycobacterium tuberculosis H37Rv for two-dimensional gel electrophoresis.

Lipophilic proteome profiling is crucial because they have an anticipated role in biological processes and pathogenesis of Mycobacterium tuberculosis. These lipophilic proteins might be used as potential targets for the development of newer diagnostic markers and drug targets due to their association with membranes and drugs. We developed an efficient and rapid method to enrich the lipophilic proteins extraction from M. tuberculosis H37Rv for 2DE. In the extraction of lipophilic proteins, nonionic detergent (Triton X-100) was added in sonication buffer that augmented the solubilization of the proteins at the time of sonication. Enriched whole cell lysate was subjected to direct phase separation using Triton X-114, without the need for preisolation of membranes. In this study, we report that our optimized extraction buffer increased the lipophilic proteins extraction and their improved resolution on 2D gel up to two- to threefolds (quantitatively and qualitatively) as compared to standard extraction buffer. Some proteins were identified by MALDI-TOF/MS.

Comparative proteomic analysis of sequential isolates of Mycobacterium tuberculosis from a patient with pulmonary tuberculosis turning from drug sensitive to multidrug resistant.

BACKGROUND & OBJECTIVES: Tuberculosis is a major health problem in India, and the emergence of multidrug resistant (MDR) and extensively drug resistant (XDR) strains of Mycobacterium tuberculosis (Mtb) has further complicated the situation. Though several studies characterizing drug sensitive and drug resistant strains are available in literature, almost all studies are done on unrelated strains. Therefore, the objective of this study was to compare the proteomic data of four sequential isolates of Mtb from a single patient who developed MDR-TB during the course of anti-tuberculosis therapy (ATT). METHODS: In this study, using two-dimensional (2D) gel electrophoresis and MALDI-TOF mass spectrometry, we compared and analyzed the cell lysate proteins of Mtb sequential clinical isolates from a patient undergoing anti-TB treatment. The mRNA expression levels of selected identified proteins were determined by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The genotypes of all four isolates remained homologous, indicating no re-infection. The initial isolate (before treatment) was sensitive to all first-line drugs, but the consecutive isolates were found to be resistant to isoniazid (INH) and rifampicin (RIF) and developed mutations in the katG, inhA and rpoB. the intensities of 27 protein spots were found to be consistently overexpressed in INH and RIF resistant isolates. The most prominent and overexpressed proteins found during the development of drug resistance were GarA (Rv1827), wag31 (Rv2145c), Rv1437 and Rv2970c. INTERPRETATION & CONCLUSIONS: This preliminary proteomic study provides an insight about the proteins that are upregulated during drug resistance development. These upregulated proteins, identified here, could prove useful as immunodiagnostic and possibly drug resistant markers in future. However, more studies are required to confirm these findings.

In silico Screening of Food and Drug Administration-approved Compounds against Trehalose 2-sulfotransferase (Rv0295c) in Mycobacterium tuberculosis: Insights from Molecular Docking and Dynamics Simulations.

BACKGROUND: Tuberculosis (TB) remains a prominent global health challenge, distinguished by substantial occurrences of infection and death. The upsurge of drug-resistant TB strains underscores the urgency to identify novel therapeutic targets and repurpose existing compounds. Rv0295c is a potentially druggable enzyme involved in cell wall biosynthesis and virulence. We evaluated the inhibitory activity of Food and Drug Administration (FDA)-approved compounds against Rv0295c of Mycobacterium tuberculosis, employing molecular docking, ADME evaluation, and dynamics simulations. METHODS: The study screened 1800 FDA-approved compounds and selected the top five compounds with the highest docking scores. Following this, we subjected the initially screened ligands to ADME analysis based on their dock scores. In addition, the compound exhibited the highest binding affinity chosen for molecular dynamics (MD) simulation to investigate the dynamic behavior of the ligand-receptor complex. RESULTS: Dihydroergotamine (CHEMBL1732) exhibited the highest binding affinity (-12.8 kcal/mol) for Rv0295c within this set of compounds. We evaluated the stability and binding modes of the complex over extended simulation trajectories. CONCLUSION: Our in silico analysis demonstrates that FDA-approved drugs can serve as potential Rv0295c inhibitors through repurposing. The combination of molecular docking and MD simulation offers a comprehensive understanding of the interactions between ligands and the protein target, providing valuable guidance for further experimental validation. Identifying Rv0295c inhibitors may contribute to new anti-TB drugs.

Exploring the Cell Wall and Secretory Proteins of Mycobacterium leprae as Biomarkers.

The bacterial cell wall is composed of a wide variety of intricate proteins in addition to lipids, glycolipids, and polymers. Given the diversity of cell wall proteins among bacterial species, they are a feasible target for biomarker identification and characterization in clinical research and diagnosis of the disease. The slow growth rate of Mycobacterium leprae poses a major hurdle in the accurate diagnosis of leprosy before the onset of peripheral neuropathy. The use of biomarker- based diagnostic methods can help in preventing the spread and manifestation of leprosy. Despite many advances in research methods and techniques, there remains a knowledge gap regarding the cell wall proteomes of M. leprae that can be used as biomarkers. The cell wall and secretory proteins of M. leprae are the major focus of this review article. This article enfolds the characteristics and functions of M. leprae cell wall proteins and gives an insight into those cell wall proteins that are yet to be established as biomarkers. Tools and techniques used in cell wall extraction and biomarker identification can also be explored in this article.

Comparative Proteomic Analysis of Capsule Proteins in Aminoglycoside-Resistant and Sensitive Mycobacterium tuberculosis Clinical Isolates: Unraveling Potential Drug Targets.

BACKGROUND: Tuberculosis (TB), a global infectious threat, has seen a concerning rise in aminoglycoside-resistant Mycobacterium tuberculosis (M.tb) strains. The potential role of capsule proteins remains largely unexplored. This layer acts as the primary barrier for tubercle bacilli, attempting to infiltrate host cells and subsequent disease development. METHODS: The study aims to bridge this gap by investigating the differentially expressed capsule proteins in aminoglycoside-resistant M.tb clinical isolates compared with drug-sensitive isolates employing two-dimensional gel electrophoresis, mass spectrometry, and bioinformatic approaches. RESULTS: We identified eight proteins that exhibited significant upregulation in aminoglycoside-resistant isolates. Protein Rv3029c and Rv2110c were associated with intermediary metabolism and respiration; Rv2462c with cell wall and cell processes; Rv3804c with lipid metabolism; Rv2416c and Rv2623 with virulence and detoxification/adaptation; Rv0020c with regulatory functions; and Rv0639 with information pathways. Notably, the Group-based Prediction System for Prokaryotic Ubiquitin-like Protein (GPS-PUP) algorithm identified potential pupylation sites within all proteins except Rv3804c. Interactome analysis using the STRING 12.0 database revealed potential interactive partners for these proteins, suggesting their involvement in aminoglycoside resistance. Molecular docking studies revealed suitable binding between amikacin and kanamycin drugs with Rv2462c, Rv3804c, and Rv2623 proteins. CONCLUSION: As a result, our findings illustrate the multifaceted nature of aminoglycoside resistance in M.tb and the importance of understanding how capsule proteins play a role in counteracting drug efficacy. Identifying the role of these proteins in drug resistance is crucial for developing more effective treatments and diagnostics for TB.

Widespread variation in molecular interactions and regulatory properties among transcription factor isoforms.

Most human Transcription factors (TFs) genes encode multiple protein isoforms differing in DNA binding domains, effector domains, or other protein regions. The global extent to which this results in functional differences between isoforms remains unknown. Here, we systematically compared 693 isoforms of 246 TF genes, assessing DNA binding, protein binding, transcriptional activation, subcellular localization, and condensate formation. Relative to reference isoforms, two-thirds of alternative TF isoforms exhibit differences in one or more molecular activities, which often could not be predicted from sequence. We observed two primary categories of alternative TF isoforms: "rewirers" and "negative regulators", both of which were associated with differentiation and cancer. Our results support a model wherein the relative expression levels of, and interactions involving, TF isoforms add an understudied layer of complexity to gene regulatory networks, demonstrating the importance of isoform-aware characterization of TF functions and providing a rich resource for further studies.

Analysis of socioeconomic condition and bacillary index with respect to the development of Hansen's disease.

Background: Leprosy is a chronic granulomatous infection caused by Mycobacterium leprae or Mycobacterium lepromatosis and mainly affects the skin and peripheral nerves. Although treatable, its early intervention can significantly reduce the occurrence of disability. India accounts for more than half of new cases globally. This study was undertaken to better understand the clinical traits of newly diagnosed cases in a tertiary facility of Western Uttar Pradesh, and a few from Madhya Pradesh and Uttarakhand. Methods: The observational prospective study was carried out on all the newly diagnosed leprosy cases who visited the Outpatient Department of ICMR-National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Agra, during October 2019-December 2022. After obtaining answers to a prestructured questionnaire with their consent, participants were enrolled in the study and underwent clinical examination and a slit-skin smear test. Results: A total of 56 cases were investigated, and among them, 20 (35.7%) and 36 (64.3%) women and men, respectively, had positive contact with persons affected by leprosy either within family, friends, or neighbors. It is observed that due to the delayed detection of leprosy cases, paucibacillary (PB) patients converted into multibacillary (MB) patients, and the number of MB cases is much higher compared to PB cases. Conclusion: Leprosy instances continue to spread frequently from sick to healthy people indicating continued transmission of leprosy in society. Multidrug therapy in the management of leprosy cases is effective; however, early diagnosis of PB cases is still a challenge and needs to be addressed on priority.

Diagnostics and Therapeutic Potential of miR-205 and miR-34a in Ovarian Cancer Management: A miRNA-Target-Based Analysis.

Epithelial ovarian cancer (EOC) treatment strategies mainly focused on surgery combined with chemotherapy. Recent targeted therapy techniques emerge as milestone and could be used for management of ovarian cancer (OC) progression with more efficacy. The aim is to evaluate the therapeutic and diagnostic potential of microRNA (miRNA) in management of EOC using in silico and quantitative real-time PCR (qRT-PCR) expression analysis. We performed functional enrichment and miRNA-Target genes expression analysis in 48 EOC and 22 normal tissue samples using qRT-PCR and correlated with miRNA expression data in matched samples to evaluate the diagnostic and therapeutic potential of miRNA in OC management. In silico functional enrichment analysis revealed miRNA association with disease. Target genes of miRNAs participate in several biologically important pathways leading to cancer progression. Targets of miRNA-205 and miRNA-34a were significantly downregulated, and upregulated, respectively, in EOC. Moreover, significant negative correlation between relative expression of miRNA-205 and target genes (BCL2, ZEB1, E2F1, and TP53) was observed with r = -0.813; r = -0.755; r = -0.559; and r = -0.767, respectively. Similarly, miRNA-34a also showed higher negative correlation with target genes (MDM4, MAPK3, BRCA1, AREG) with r = -0.840; r = -0.870; r = -0.622; and r = -0.623, respectively. In addition, receiver operating characteristics analysis of combined miRNA panel, miRNA-205-Target gene panel, and miRNA-34a-Target gene panel exhibited higher diagnostics value with area under the curve (AUC) of 92.7 (p < 0.0001), 94.8 (p < 0.0001), and 98.3 (p < 0.0001), respectively. Negative Correlation between miRNA and target genes expression data in matched samples highlights therapeutic potential of miRNA in EOC management. Moreover, combined diagnostic potential of miRNA-target gene panel could predict risk of EOC with higher AUC, sensitivity, and specificity.