{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T14:46:30Z","timestamp":1785941190390,"version":"3.56.0"},"reference-count":44,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Non-Coding RNA","ncRNA"],"abstract":"<jats:p>Background: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that affects women of reproductive age, often associated with metabolic issues, causing infertility. Although it is common, the cause of PCOS remains unknown, and early diagnosis is challenging. MicroRNAs (miRNAs) serve as post-transcriptional regulators of gene expression, play a significant role in PCOS development, and have emerged as biomarkers for reproductive and metabolic disorders. However, research on miRNA signatures in the Indian population is limited. This pilot exploratory study aims to compare the candidate differentially expressed miRNAs (DE miRNAs) in serum samples from individuals with and without PCOS using high-throughput miRNA sequencing. Methods: In the study, patients with PCOS and age-matched controls were included; small RNAs were isolated from their serum, libraries were prepared, and the libraries were analyzed by next-generation sequencing. Bioinformatics analysis, including miRBase annotation, differential expression analysis, target prediction, GO\/KEGG enrichment, and hub gene network analysis, was performed. Results: A total of 967 miRNAs were identified, with seven showing differential expression (log2FC &gt; 1, p &lt; 0.05). Among these, six miRNAs of hsa-miR-219a-2-3p, hsa-mir-384, hsa-miR-149-5p, hsa-miR-3182, hsa-miR-3960, and hsa-miR-4508 were upregulated, whereas hsa-mir-139 was downregulated. Functional enrichment and hub gene analyses identified key targets, including TP53, FOXO1, HIF1A, and HDAC1, that are crucial to the cell cycle, insulin signaling, and hypoxia. Conclusions: These preliminary findings identify candidate serum miRNA signatures in Indian women that may be associated with PCOS\u2019s reproductive and metabolic issues. These pilot study results suggest potential miRNAs and their target pathway links with PCOS that need validation in larger cohorts for diagnostic or therapeutic applications.<\/jats:p>","DOI":"10.3390\/ncrna12040030","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T13:16:29Z","timestamp":1785935789000},"page":"30","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An Exploratory Study on Transcriptomic Profiling of Circulating miRNA Associated with Hub Genes in the Development of Polycystic Ovary Syndrome"],"prefix":"10.3390","volume":"12","author":[{"given":"Yogesh","family":"Vetriselvan","sequence":"first","affiliation":[{"name":"Department of Medical Biotechnology, Faculty of Interdisciplinary Studies, Aarupadai Veedu Medical College and Hospital, Vinayaka Mission\u2019s Research Foundation (DU), Kirumampakkam, Puducherry 607403, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1370-9330","authenticated-orcid":false,"given":"Jayakumar","family":"Swetha","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Aarupadai Veedu Medical College and Hospital, Vinayaka Mission\u2019s Research Foundation (DU), Kirumampakkam, Puducherry 607403, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manoranjani","family":"Murugan","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology, Faculty of Interdisciplinary Studies, Aarupadai Veedu Medical College and Hospital, Vinayaka Mission\u2019s Research Foundation (DU), Kirumampakkam, Puducherry 607403, India"},{"name":"Central Research Laboratory, Vinayaka Mission\u2019s Sankarachariyar Dental College, Salem 636308, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4177-024X","authenticated-orcid":false,"given":"Irisappan","family":"Ganesh","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology, Faculty of Interdisciplinary Studies, Aarupadai Veedu Medical College and Hospital, Vinayaka Mission\u2019s Research Foundation (DU), Kirumampakkam, Puducherry 607403, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8856-7348","authenticated-orcid":false,"given":"Vishnu Bhat","family":"Ballambattu","sequence":"additional","affiliation":[{"name":"Medical Research and Publications, Aarupadai Veedu Medical College and Hospital, Vinayaka Mission\u2019s Research Foundation (DU), Kirumampakkam, Puducherry 607403, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pushpa Premanath","family":"Kotur","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Aarupadai Veedu Medical College and Hospital, Vinayaka Mission\u2019s Research Foundation (DU), Kirumampakkam, Puducherry 607403, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepa","family":"Shanmugam","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Aarupadai Veedu Medical College and Hospital, Vinayaka Mission\u2019s Research Foundation (DU), Kirumampakkam, Puducherry 607403, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5336-1895","authenticated-orcid":false,"given":"Marcella Sherin","family":"Samuel","sequence":"additional","affiliation":[{"name":"Sandbox Innovation Fund Program, Massachusetts Institute of Technology, iHQ (Bldg E38), 292 Main St, Cambridge, MA 02142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7351-0421","authenticated-orcid":false,"given":"Sambandam","family":"Ravikumar","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology, Faculty of Interdisciplinary Studies, Aarupadai Veedu Medical College and Hospital, Vinayaka Mission\u2019s Research Foundation (DU), Kirumampakkam, Puducherry 607403, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1093\/humrep\/dey256","article-title":"Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome","volume":"33","author":"Teede","year":"2018","journal-title":"Hum. Reprod."},{"key":"ref_2","first-page":"16637","article-title":"Serum expression levels of selected microRNAs and their association with glucose metabolism in young women with polycystic ovary syndrome","volume":"134","author":"Krentowska","year":"2024","journal-title":"Pol. Arch. Intern. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.1093\/humrep\/dew218","article-title":"The prevalence and phenotypic features of polycystic ovary syndrome: A systematic review and meta-analysis","volume":"31","author":"Bozdag","year":"2016","journal-title":"Hum. Reprod."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Cirillo, F., Catellani, C., Lazzeroni, P., Sartori, C., Nicoli, A., Amarri, S., La Sala, G.B., and Street, M.E. (2019). MiRNAs Regulating Insulin Sensitivity Are Dysregulated in Polycystic Ovary Syndrome (PCOS) Ovaries and Are Associated with Markers of Inflammation and Insulin Sensitivity. Front. Endocrinol., 10.","DOI":"10.3389\/fendo.2019.00879"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e10998","DOI":"10.7717\/peerj.10998","article-title":"High throughput microRNAs sequencing profile of serum exosomes in women with and without polycystic ovarian syndrome","volume":"9","author":"Zhang","year":"2021","journal-title":"PeerJ"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1111\/j.1399-0004.2008.01076.x","article-title":"MicroRNAs in development and disease","volume":"74","author":"Erson","year":"2008","journal-title":"Clin. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Kyriazi, A.A., Papiris, E., Kitsos Kalyvianakis, K., Sakellaris, G., and Baritaki, S. (2020). Dual Effects of Non-Coding RNAs (ncRNAs) in Cancer Stem Cell Biology. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186658"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0092-8674(04)00045-5","article-title":"MicroRNAs: Genomics, biogenesis, mechanism, and function","volume":"116","author":"Bartel","year":"2004","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1080\/09513590.2018.1428299","article-title":"Serum miRNAs in women affected by hyperandrogenic polycystic ovary syndrome: The potential role of miR-155 as a biomarker for monitoring the estroprogestinic treatment","volume":"34","author":"Arancio","year":"2018","journal-title":"Gynecol. Endocrinol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1016\/j.fertnstert.2014.08.005","article-title":"Molecular characterization of exosomes and their microRNA cargo in human follicular fluid: Bioinformatic analysis reveals that exosomal microRNAs control pathways involved in follicular maturation","volume":"102","author":"Santonocito","year":"2014","journal-title":"Fertil. Steril."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1016\/j.fertnstert.2013.10.042","article-title":"MicroRNA: Key gene expression regulators","volume":"101","author":"Vilella","year":"2014","journal-title":"Fertil. Steril."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Shen, K.Y., Dai, X.L., Li, S., Huang, F., Chen, L.Q., Luo, P., and Qu, X.L. (2023). Specific expression profile of follicular fluid-derived exosomal microRNAs in patients with diminished ovarian reserve. BMC Med. Genom., 16.","DOI":"10.1186\/s12920-023-01756-9"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"100131","DOI":"10.1016\/j.ocarto.2020.100131","article-title":"A bioinformatics approach to microRNA-sequencing analysis","volume":"3","author":"Potla","year":"2021","journal-title":"Osteoarthr. Cartil. Open"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s12958-021-00706-3","article-title":"Identification of key pathways and genes in polycystic ovary syndrome via integrated bioinformatics analysis and prediction of small therapeutic molecules","volume":"19","author":"Devarbhavi","year":"2021","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1080\/09513590.2018.1460341","article-title":"Increased risk of polycystic ovary syndrome (PCOS) associated with CC genotype of miR-146a gene variation","volume":"34","author":"Ebrahimi","year":"2018","journal-title":"Gynecol. Endocrinol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1007\/s40618-021-01498-4","article-title":"Conceptualization of functional single nucleotide polymorphisms of polycystic ovarian syndrome genes: An in silico approach","volume":"44","author":"Prabhu","year":"2021","journal-title":"J. Endocrinol. Investig."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Teede, H., Deeks, A., and Moran, L. (2010). Polycystic ovary syndrome: A complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC Med., 8.","DOI":"10.1186\/1741-7015-8-41"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"92","DOI":"10.3892\/br.2023.1674","article-title":"Differential expression of plasma derived exosomal miRNAs in polycystic ovary syndrome as a circulating biomarker","volume":"19","author":"Liu","year":"2023","journal-title":"Biomed. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"137","DOI":"10.33594\/000000622","article-title":"miRNA-mRNA Network in PBMCs of PCOS Women Identifies Overactivated Stress-Activated Kinases","volume":"57","author":"Krishna","year":"2023","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1186\/s12967-025-07628-3","article-title":"Novel serum small extracellular vesicle miRNAs with multi-target RCA-CRISPR sensor for liver cancer detection","volume":"24","author":"Fan","year":"2026","journal-title":"J. Transl. Med."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Cui, W., Xuan, T., Liao, T., and Wang, Y. (2024). From sequencing to validation: NGS-based exploration of plasma miRNA in papillary thyroid carcinoma. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1410110"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/s41420-022-01136-9","article-title":"Circular RNA circPOSTN promotes neovascularization by regulating miR-219a-2-3p\/STC1 axis and stimulating the secretion of VEGFA in glioblastoma","volume":"8","author":"Long","year":"2022","journal-title":"Cell Death Discov."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/j.biopha.2018.09.110","article-title":"MicroRNA-384 inhibits the progression of esophageal squamous cell carcinoma through blockade of the LIMK1\/cofilin signaling pathway by binding to LIMK1","volume":"109","author":"Yu","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"108822","DOI":"10.1016\/j.biopha.2019.108822","article-title":"MicroRNA-384 is lowly expressed in human prostate cancer cells and has anti-tumor functions by acting on HOXB7","volume":"114","author":"Hong","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Kargun, K., Aygen, E., Ebiloglu, M.F., Alayunt, N.O., and Dalkilic, L.K. (2025). Evaluation of miRNA Profile and Its Relationship with Metabolic Disorders in Obese and Pre-Obese Patients. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47040280"},{"key":"ref_26","first-page":"2","article-title":"hsa-miR-149-5p diminish MAPK and PI3K\/Akt signalling pathways through down-regulation of ERbB3 in SLE patients","volume":"7","author":"Ghods","year":"2018","journal-title":"Mol. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ren, F.J., Yao, Y., Cai, X.Y., Cai, Y.T., Su, Q., and Fang, G.Y. (2021). MiR-149-5p: An Important miRNA Regulated by Competing Endogenous RNAs in Diverse Human Cancers. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.743077"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"952","DOI":"10.3390\/cimb44020063","article-title":"MicroRNA-22-3p and MicroRNA-149-5p Inhibit Human Hepatocellular Carcinoma Cell Growth and Metastasis Properties by Regulating Methylenetetrahydrofolate Reductase","volume":"44","author":"Li","year":"2022","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"El-Shqnqery, H.E., Mohamed, R.H., Samir, O., Ayoub, I., El-Sayed, W.M., and Sayed, A.A. (2023). miRNome of Child A hepatocellular carcinoma in Egyptian patients. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1137585"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Zalewski, D.P., Ruszel, K., St\u0119pniewski, A., Ga\u0142kowski, D., Feldo, M., Kocki, J., and Bogucka-Kocka, A. (2022). Relationships between indicators of lower extremity artery disease and miRNA expression in peripheral blood mononuclear cells. J. Clin. Med., 11.","DOI":"10.3390\/jcm11061619"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Kwon, M.J., Park, H.Y., Lee, J.S., Kim, E.S., Kim, N.Y., Nam, E.S., Cho, S.J., and Kang, H.S. (2023). Dysregulated microRNA Expression Relevant to TERT Promoter Mutations in Tonsil Cancer\u2014A Pilot Study. Life, 13.","DOI":"10.3390\/life13102090"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1016\/j.jvs.2014.10.099","article-title":"Altered microRNA expression in stenoses of native arteriovenous fistulas in hemodialysis patients","volume":"63","author":"Lv","year":"2016","journal-title":"J. Vasc. Surg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3522492","DOI":"10.1155\/2022\/3522492","article-title":"circHtra1\/miR-3960\/GRB10 Axis Promotes Neuronal Loss and Immune Deficiency in Traumatic Brain Injury","volume":"2022","author":"Zheng","year":"2022","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Brancaccio, M., Giachino, C., Iazzetta, A.M., Cordone, A., De Marino, E., Affinito, O., Vivo, M., Calabr\u00f2, V., Pollice, A., and Angrisano, T. (2022). Integrated bioinformatics analysis reveals novel miRNA as biomarkers associated with preeclampsia. Genes, 13.","DOI":"10.3390\/genes13101781"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1159\/000494168","article-title":"Circulating miRNA Expression Profiling and Target Prediction in Patients Receiving Dexmedetomidine","volume":"50","author":"Yang","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e23945","DOI":"10.1002\/jcla.23945","article-title":"Abnormal regulation of microRNAs and related genes in pediatric beta-thalassemia","volume":"35","author":"Wang","year":"2021","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"D155","DOI":"10.1093\/nar\/gky1141","article-title":"miRBase: From microRNA sequences to function","volume":"47","author":"Kozomara","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_38","first-page":"10","article-title":"Differential analysis of count data\u2013the DESeq2 package","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e05005","DOI":"10.7554\/eLife.05005","article-title":"Predicting effective microRNA target sites in mammalian mRNAs","volume":"4","author":"Agarwal","year":"2015","journal-title":"eLife"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"D447","DOI":"10.1093\/nar\/gku1003","article-title":"STRING v10: Protein-protein interaction networks, integrated over the tree of life","volume":"43","author":"Szklarczyk","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Chin, C.H., Chen, S.H., Wu, H.H., Ho, C.W., Ko, M.T., and Lin, C.Y. (2014). cytoHubba: Identifying hub objects and sub-networks from complex interactome. BMC Syst. Biol., 8.","DOI":"10.1186\/1752-0509-8-S4-S11"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"D988","DOI":"10.1093\/nar\/gkab1049","article-title":"Ensembl 2022","volume":"50","author":"Cunningham","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Chen, E.Y., Tan, C.M., Kou, Y., Duan, Q., Wang, Z., Meirelles, G.V., Clark, N.R., and Ma\u2019ayan, A. (2013). Enrichr: Interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinform., 14.","DOI":"10.1186\/1471-2105-14-128"}],"container-title":["Non-Coding RNA"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2311-553X\/12\/4\/30\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T13:48:55Z","timestamp":1785937735000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2311-553X\/12\/4\/30"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,5]]},"references-count":44,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ncrna12040030"],"URL":"https:\/\/doi.org\/10.3390\/ncrna12040030","relation":{},"ISSN":["2311-553X"],"issn-type":[{"value":"2311-553X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,5]]}}}