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Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer
Published on: August 2, 2024
MicroRNA expression profiles in non‑epithelial ovarian tumors
Roger K Chang1, Xidan Li2, Ninni Mu1
1Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
Abstract:
Ovarian germ cell tumors (OGCTs) and sex cord stromal tumors (SCSTs) are rare gynecologic tumors that are derived from germ and stromal cells, respectively. Unlike their epithelial counterparts, molecular pathogenesis of these tumor types is still poorly understood. Here, we characterized microRNA (miRNA) expression profiles of 9 OGCTs (2 malignant and 7 benign) and 3 SCSTs using small RNA sequencing. We observed significant miRNA expression variations among the three tumor groups. To further demonstrate the biological relevance of our findings, we selected 12 miRNAs for validation in an extended cohort of 16 OGCTs (9 benign and 7 malignant) and 7 SCSTs by reverse transcription-quantitative polymerase chain reaction. Higher expression of miR‑373‑3p, miR‑372‑3p and miR‑302c‑3p and lower expression of miR‑199a‑5p, miR‑214‑5p and miR‑202‑3p were reproducibly observed in malignant OGCTs as compared to benign OGCTs or SCSTs. Comparing with benign OGCTs, miR‑202c‑3p and miR‑513c‑5p were more abundant in SCSTs. Additionally, we examined Beclin 1 (BECN1), a target of miR‑199a‑5p, in the clinical samples using western blot analysis. Our results show that BECN1 expression was higher in malignant OGCTs than benign OGCTs, which is concordant with their lower miR‑199a‑5p expression. This study suggests that these miRNAs may have potential value as tumor markers and implications for further understanding the molecular basis of these tumor types.
Insights
This study investigated microRNA (miRNA) expression in rare ovarian germ cell tumors (OGCTs) and sex cord stromal tumors (SCSTs). Specific miRNA profiles, like higher miR-373-3p in malignant OGCTs, may serve as ovarian cancer biomarkers.
Area of Science:
- Gynecologic Oncology
- Molecular Pathology
- Genomics
Background:
- Ovarian germ cell tumors (OGCTs) and sex cord stromal tumors (SCSTs) are rare gynecologic neoplasms.
- Their molecular pathogenesis remains poorly understood compared to epithelial ovarian cancers.
Purpose of the Study:
- To characterize microRNA (miRNA) expression profiles in OGCTs and SCSTs.
- To identify potential miRNA biomarkers for distinguishing tumor types and malignancy.
Main Methods:
- Small RNA sequencing was used to analyze miRNA expression in 9 OGCTs and 3 SCSTs.
- Quantitative reverse transcription PCR validated miRNA expression in an extended cohort (16 OGCTs, 7 SCSTs).
- Western blot analysis assessed Beclin 1 (BECN1) expression in relation to miRNA levels.
Main Results:
- Significant miRNA expression variations were observed across OGCTs and SCSTs.
- Malignant OGCTs showed higher expression of miR-373-3p, miR-372-3p, miR-302c-3p and lower expression of miR-199a-5p, miR-214-5p, miR-202-3p compared to benign OGCTs or SCSTs.
- SCSTs exhibited higher miR-202c-3p and miR-513c-5p than benign OGCTs. BECN1 expression was elevated in malignant OGCTs, inversely correlating with miR-199a-5p levels.
Conclusions:
- Specific miRNA signatures differentiate OGCTs and SCSTs, and correlate with malignancy in OGCTs.
- These miRNAs hold potential as diagnostic biomarkers for ovarian tumors.
- The findings offer insights into the molecular mechanisms underlying OGCT and SCST development.
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