MiR-5195-3p functions as a tumor suppressor by targeting RHBDD1 in ovarian cancer
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Zhanyu Wang [1] ; Xiaoping Zhang [1] ; Yongying Liu [1] ; Xiaoyan Shi [1] ; Lijun Li [1] ; Yun Jia [1] ; Fangfang Wu [1] ; Haosen Cui [1] ; Liang Li [1]
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[1] Anhui Medical University
Anhui Medical University
China
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- Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 38, Nº. 12, 2023, págs. 1403-1413
- Idioma: inglés
- Enlaces
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Resumen
Background. Recent studies have reported the tumor suppressive role of miR-5195-3p in the progression of several cancers, but the potential roles of miR-5195-3p in ovarian cancer (OC) remain largely unknown.
Methods. We first analyzed the expression levels of miR-5195-3p in 83 pairs of human OC tissues and adjacent specimens by reverse transcription-quantitative PCR. The correlation of miR-5195-3p/rhomboid domain containing 1 (RHBDD1) and clinicopathological parameters was analyzed by chi-square test. The prognostic value of miR-5195-3p was evaluated by Kaplan-Meier method Cox proportional hazards models.
The effects of miR-5195-3p on cell proliferation, cell cycle distribution, migration and invasion were examined by CCK-8 assay, colony formation assay, flow cytometry and transwell assay. Tumor forming was evaluated by nude mice model in vivo. The association between miR-5195-3p and RHBDD1 was verified by luciferase reporter assay.
Results. We observed that miR-5195-3p level was remarkably reduced in OC tissues as compared to adjacent tissues. The expression of miR-5195-3p was associated with FIGO stage, depth of invasion and poor survival prognosis in OC patients. Overexpression of miR-5195-3p significantly suppressed cell proliferation, cell cycle G1/S transition, migration and invasion in OC cell lines (SKOV-3 and OVCAR3), while knockdown of miR-5195-3p obtained the opposite results. We further confirmed miR-5195-3p as a negative posttranscriptional modulator of RHBDD1. RHBDD1 expression was upregulated in OC tissues compared with adjacent tissues, which was inversely correlated with miR-5195-3p expression. The expression of RHBDD1 was associated with FIGO stage and distant metastasis.
RHBDD1 overexpression reversed the suppressive role of miR-5195-3p on OC cell proliferation, migration and invasion. Consistent with the in vitro results, miR-5195- 3p overexpression decreased the growth of subcutaneously inoculated tumors in nude mice.
Conclusions. Taken together, the present results indicated that miR-5195-3p acts a tumor suppressor by targeting RHBDD1 in OC.
