Targeting miR-506 in leiomyosarcoma therapy: simultaneous suppression of metastatic potential and potentiation of pirarubicin efficacy.
5 affiliations
- 1Department of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Institute and Cancer Hospital, Tianjin, China.
- 2State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin, China.
- 3Key Laboratory of Molecular Cancer Epidemiology, Tianjin, China.
- 4National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
- 5Department of Obstetrics and Gynecology, the Fourth Hospital of Shijiazhuang, Shijiazhuang, China.
Abstract
Extensive studies have established that miR-506 inhibits epithelial-mesenchymal transition (EMT) in epithelial ovarian cancer by upregulating E-cadherin while suppressing vimentin and N-cadherin. Additionally, miR-506 has been shown to enhance the therapeutic response of serous ovarian cancer to cisplatin and olaparib via modulation of RAD51. However, the functional role of miR-506 in leiomyosarcoma (LMS) remains unexplored. This study aims to investigate the expression and functional role of miR-506 in soft tissue LMS, focusing on its clinical relevance and impact on tumor progression and chemosensitivity. We conducted a retrospective study of 61 Chinese patients diagnosed with soft tissue LMS between January 2000 and December 2012. Survival outcomes were assessed using Kaplan-Meier analysis with log-rank tests for statistical comparison. Furthermore, in vitro functional assays were performed to elucidate the role of miR-506 in soft tissue LMS pathogenesis and its underlying mechanism in modulating chemosensitivity. Our findings demonstrated significantly downregulated miR-506 expression in tumor tissues compared with normal controls, with higher miR-506 expression associated with improved overall survival (OS). In our cohort of 61 LMS patients, Kaplan-Meier analysis revealed that positive expression of N-cadherin and vimentin correlated with poorer clinical outcomes. Similarly, elevated expression of DNA repair proteins (RAD51, RAD52, ATM, and ATR) was associated with reduced OS. In vitro functional studies showed that miR-506 upregulated epithelial markers (E-cadherin and β-catenin) while suppressing mesenchymal markers (vimentin and N-cadherin), consequently inhibiting LMS cell proliferation, migration, and invasion. Moreover, miR-506 enhanced pirarubicin sensitivity by dual mechanisms: (I) By downregulating DNA damage homologous repair proteins (ATM, ATR, RAD51, and RAD52), and (II) modulating EMT via targeting EMT-associated regulatory protein Slug and mesenchymal marker vimentin. Our study demonstrates that miR-506 induces mesenchymal-epithelial transition-like phenotypic changes in vitro and modulates homologous recombination repair pathways, effectively inhibiting LMS cell proliferation, migration, and invasion while enhancing chemosensitivity.
Related
- Leiomyosarcoma Involving the Calcaneum With Delayed Gastric and Sacroiliac Lesions: A Case Report
- Nasopharyngeal Leiomyosarcoma: Diagnostic Challenges and Management of a Rare Head and Neck Sarcoma
- From Unexplained Iron-Deficiency Anaemia to Ileo-Ileal Intussusception: A Case Report of Primary Small Bowel Leiomyosarcoma
- Plantar cutaneous leiomyosarcoma: an entity of rare presentation and diagnostic challenge☆
- Pararectal Leiomyosarcoma Following Total Laparoscopic Hysterectomy (TLH) for Initially Diagnosed Uterine Leiomyoma
BibTeX
@article{li2026targeting,
title = {{Targeting miR-506 in leiomyosarcoma therapy: simultaneous suppression of metastatic potential and potentiation of pirarubicin efficacy.}},
author = {Ting Li and Ruwei Xing and Feng Li and Jilong Yang},
journal = {Translational cancer research},
year = {2026},
month = sep,
doi = {10.21037/tcr-2026-1559},
url = {https://europepmc.org/article/MED/42997687},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Targeting miR-506 in leiomyosarcoma therapy: simultaneous suppression of metastatic potential and potentiation of pirarubicin efficacy.
AU - Ting Li
AU - Ruwei Xing
AU - Feng Li
AU - Jilong Yang
PY - 2026
DA - 2026/09/28
JO - Translational cancer research
DO - 10.21037/tcr-2026-1559
UR - https://europepmc.org/article/MED/42997687
AB - Extensive studies have established that miR-506 inhibits epithelial-mesenchymal transition (EMT) in epithelial ovarian cancer by upregulating E-cadherin while suppressing vimentin and N-cadherin. Additionally, miR-506 has been shown to enhance the therapeutic response of serous ovarian cancer to cisplatin and olaparib via modulation of RAD51. However, the functional role of miR-506 in leiomyosarcoma (LMS) remains unexplored. This study aims to investigate the expression and functional role of miR-506 in soft tissue LMS, focusing on its clinical relevance and impact on tumor progression and chemosensitivity. We conducted a retrospective study of 61 Chinese patients diagnosed with soft tissue LMS between January 2000 and December 2012. Survival outcomes were assessed using Kaplan-Meier analysis with log-rank tests for statistical comparison. Furthermore, in vitro functional assays were performed to elucidate the role of miR-506 in soft tissue LMS pathogenesis and its underlying mechanism in modulating chemosensitivity. Our findings demonstrated significantly downregulated miR-506 expression in tumor tissues compared with normal controls, with higher miR-506 expression associated with improved overall survival (OS). In our cohort of 61 LMS patients, Kaplan-Meier analysis revealed that positive expression of N-cadherin and vimentin correlated with poorer clinical outcomes. Similarly, elevated expression of DNA repair proteins (RAD51, RAD52, ATM, and ATR) was associated with reduced OS. In vitro functional studies showed that miR-506 upregulated epithelial markers (E-cadherin and β-catenin) while suppressing mesenchymal markers (vimentin and N-cadherin), consequently inhibiting LMS cell proliferation, migration, and invasion. Moreover, miR-506 enhanced pirarubicin sensitivity by dual mechanisms: (I) By downregulating DNA damage homologous repair proteins (ATM, ATR, RAD51, and RAD52), and (II) modulating EMT via targeting EMT-associated regulatory protein Slug and mesenchymal marker vimentin. Our study demonstrates that miR-506 induces mesenchymal-epithelial transition-like phenotypic changes in vitro and modulates homologous recombination repair pathways, effectively inhibiting LMS cell proliferation, migration, and invasion while enhancing chemosensitivity.
SN - 2218-676X
SN - 2219-6803
ER -