Han Yunwei, Li Weidong, Zhi Renyong, Ma Gui, Gao Ang, Wu Kailiang, Sun Hui, Zhao Dan, Yang Yiling, Liu Fangfang, Gu Feng, Guo Xiaojing, Dong Jintang, Li Shuai, Fu Li
Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
National Clinical Research Center of Cancer, Tianjin 300060, China.
Heliyon. 2024 Jul 2;10(13):e33938. doi: 10.1016/j.heliyon.2024.e33938. eCollection 2024 Jul 15.
Invasive micropapillary carcinoma (IMPC) of the breast has a high propensity for lymphovascular invasion and axillary lymph node metastasis and displays an 'inside-out' growth pattern, but the molecular mechanism of invasion, metastasis and cell polarity reversal in IMPC is unclear.
and Patients: Cell growth curves, tumor sphere formation assays, transwell assays, mouse xenograft model and immunofluorescence were evaluated to investigate the effects of miR-30c and MTDH. Dual luciferase reporter assays was performed to confirm that the MTDH (metadherin) 3'UTR bound to miR-30c. MiRNA hybridization (ISH) and immunohistochemistry (IHC) were carried out on IMPC patient tissues for miR-30c and MTDH expression, respectively.
We found miR-30c as a tumor suppressor gene in cell proliferation, metastasis and polarity reversal of IMPC. Overexpression of miR-30c inhibited cell growth and metastasis and . MiR-30c could directly target the MTDH 3'UTR. MiR-30c overexpression inhibited breast cancer cell proliferation, invasion and metastasis by targeting MTDH. Moreover, miR-30c/MTDH axis could also regulate cell polarity reversal of IMPC. By ISH and IHC analyses, miR-30c and MTDH were significantly correlated with tumor size, lymph nodule status and tumor grade, the 'inside-out' growth pattern, overall survival (OS) and disease-free survival (DFS) in IMPC patients.
Overall, miR-30c/MTDH axis was responsible for tumor proliferation, metastasis and polarity reversal. It may provide promising therapeutic targets and prognostic biomarkers for patients with IMPC.
乳腺浸润性微乳头状癌（IMPC）具有较高的淋巴管侵犯和腋窝淋巴结转移倾向，并呈现“由内向外”的生长模式，但IMPC中侵袭、转移和细胞极性逆转的分子机制尚不清楚。
对患者进行细胞生长曲线、肿瘤球形成试验、Transwell试验、小鼠异种移植模型和免疫荧光检测，以研究miR-30c和MTDH的作用。进行双荧光素酶报告基因检测以证实MTDH（黏附素）3'UTR与miR-30c结合。分别对IMPC患者组织进行miRNA杂交（ISH）和免疫组织化学（IHC）检测miR-30c和MTDH的表达。
我们发现miR-30c是IMPC细胞增殖、转移和极性逆转中的肿瘤抑制基因。miR-30c的过表达抑制细胞生长和转移。miR-30c可直接靶向MTDH 3'UTR。miR-30c过表达通过靶向MTDH抑制乳腺癌细胞增殖、侵袭和转移。此外，miR-30c/MTDH轴还可调节IMPC的细胞极性逆转。通过ISH和IHC分析，miR-30c和MTDH与IMPC患者的肿瘤大小、淋巴结状态、肿瘤分级、“由内向外”生长模式、总生存（OS）和无病生存（DFS）显著相关。
总体而言，miR-30c/MTDH轴负责肿瘤增殖、转移和极性逆转。它可能为IMPC患者提供有前景的治疗靶点和预后生物标志物。
