Abstract
The incidence rate of developing ovarian cancer decreases over the years; however, mortality ranks top among malignancies of women, mainly metastasis through local invasion. Matrilin-2 (MATN2) is a member of the matrilin family that plays an important role in many cancers. However, its relationship with ovarian cancer remains unknown. Our study aimed to explore the function and possible mechanism of MATN2 in ovarian cancer. Human ovarian cancer tissue microarrays were used to detect the MATN2 expression in different types of ovarian cancer using immunohistochemistry (IHC). CCK-8, wound scratch healing assay, transwell assay, and flow cytometry were used to detect cell mobility. Gene and protein expression were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. MATN2 interacts with phosphatase, and the tensin homolog (PTEN) deleted on chromosome 10 was analyzed using TCGA database and co-immunoprecipitation (Co-IP). In vivo experiments were conducted using BALB/c nude mice, and tumor volume and weight were recorded. Tumor growth was determined using hematoxylin and eosin (H&E) and IHC staining. MATN2 was significantly downregulated in ovarian cancer cells. The SKOV3 and A2780 cell mobility was significantly inhibited by MATN2 overexpression, while the cell apoptosis rate was significantly increased. MATN2 overexpression decreased transplanted tumor size in vivo. These results were reversed by inhibiting MATN2. Furthermore, we found that PTEN closely interacted with MATN2 using bioinformatics and Co-IP. MATN2 overexpression significantly inhibited the PI3K/AKT pathway, however, PTEN suppression reversed this effect of MATN2 overexpression. These results indicated that MATN2 may play a critical role in ovarian cancer development by inhibiting cells proliferation and migration. The mechanism was related to interacting with PTEN, thus inhibiting downstream effectors in the PI3K/AKT pathway, which may be a novel target for treating ovarian cancer.
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The dataset used and/or analyzed in this study is available from the corresponding author on reasonable request.
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Funding
This study was financially supported by the Natural Key Project of Bengbu Medical College (2020byzd063).
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Conceived and designed the study: Jingbo Liu, Youguo Chen.
Performed the literature search and data extraction: Jingbo Liu, Jing Zhang, Bo Yang.
Analyzed the data: Jingbo Liu, Hongli Liu, Yuan Zhang.
Drafted the manuscript: Jingbo Liu.
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The experimental protocols were approved by the Ethics Committee of Bengbu Medical College (approval number: 2021[144]). Informed consent to participate was obtained from the patients.
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The study protocol was approved by the Animal Ethics Committee of Bengbu Medical College (approval number: 2021[236]).
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Liu, J., Zhang, J., Zhang, Y. et al. MATN2 overexpression suppresses tumor growth in ovarian cancer via PTEN/PI3K/AKT pathway. Funct Integr Genomics 24, 71 (2024). https://doi.org/10.1007/s10142-024-01340-z
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DOI: https://doi.org/10.1007/s10142-024-01340-z