Department of Obstetrics and Gynecology, Southwest Hospital, Third Military Medical University, Chongqing, Sichuan , China.
Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Bioengineered. 2022 May;13(5):12030-12044. doi: 10.1080/21655979.2022.2056314.
Ovarian cancer (OC) has the highest mortality rate among gynecological cancers, which progresses owing to dysregulated microRNAs (miRNAs) expression. Our study attempts to reveal the mechanism by which decreased miR-324-3p expression suppresses OC proliferation. Quantitative real-time PCR, western blotting, in situ hybridization, and immunohistochemistry were performed to estimate miR-324-3p and WNK2 expression levels in OC cells and tissues. Cell Counting Kit-8, colony formation, EdU, and transwell assays were performed to analyze the influence of miR-324-3p and WNK2 on the proliferation and invasion ability of OC cells. Subsequently, xenograft models were established to examine the effects of WNK2 on OC cell proliferation in vivo, and databases and luciferase reporter assays were used to test the relationship between miR-324-3p and expression. Then, we showed that miR-324-3p expression is decreased in OC cells and tissues, indicating its inhibitory effect on OC cell proliferation. Quantitative real-time PCR and luciferase reporter assays demonstrated that miR-324-3p inhibited expression by directly binding to its 3' untranslated region. WNK2, an upregulated kinase, promotes the proliferation and invasion of OC cells by activating the RAS pathway. Moreover, WNK2 can partly reverse the inhibitory effects of miR-324-3p on OC cell proliferation. Hence, we demonstrate that miR-324-3p suppressed ovarian cancer progression by targeting the /RAS pathway. Our study provides theoretical evidence for the clinical application potential of miR-324-3p.
卵巢癌（OC）是妇科癌症中死亡率最高的癌症，其进展是由于 microRNAs（miRNAs）表达失调所致。我们的研究试图揭示 miR-324-3p 表达下调抑制 OC 增殖的机制。通过定量实时 PCR、western blot、原位杂交和免疫组织化学分析 OC 细胞和组织中 miR-324-3p 和 WNK2 的表达水平。通过细胞计数试剂盒-8、集落形成、EdU 和 Transwell 测定分析 miR-324-3p 和 WNK2 对 OC 细胞增殖和侵袭能力的影响。随后，建立异种移植模型以体内检测 WNK2 对 OC 细胞增殖的影响，并使用数据库和荧光素酶报告测定来测试 miR-324-3p 和 表达之间的关系。然后，我们表明 miR-324-3p 在 OC 细胞和组织中的表达降低，表明其对 OC 细胞增殖具有抑制作用。定量实时 PCR 和荧光素酶报告测定表明，miR-324-3p 通过直接结合其 3'非翻译区抑制 表达。WNK2 是一种上调的激酶，通过激活 RAS 通路促进 OC 细胞的增殖和侵袭。此外，WNK2 可以部分逆转 miR-324-3p 对 OC 细胞增殖的抑制作用。因此，我们证明 miR-324-3p 通过靶向 /RAS 通路抑制卵巢癌进展。我们的研究为 miR-324-3p 的临床应用潜力提供了理论依据。
