三陰性乳癌缺少了早期診斷的生物標誌以及有效的標靶治療。由於無效的化療效果和高度轉移能力，因此了解抗藥性和轉移的機轉對於三陰性乳癌病患來說，是一個重要的課題。微核醣核酸(miRNAs)經常在乳癌調控失常，且影響廣泛的組織，單獨或合併循環性microRNAs可能可以當作診斷、預測和預後的生物標誌，以及治療標的。在本研究中，我們運用ROC曲線分析，發現到循環性miR-105/93-3p可以在三陰性乳癌中當作診斷的生物標誌 (AUC分別為0.928和0.657)。從1299乳癌病患的微晶片資料庫中，我們發現miR-301b, miR-181a-3p, miR-105和miR-93-3p有異常表現，且相關於三陰性乳癌病患的預後不良。我們在細胞內過度表現或抑制這些微核醣核酸來研究他們在癌化的過程。在它們之中，miR-93-3p和miR-105可以促進三陰性乳癌細胞的細胞幹性、化療抗性和轉移。miR-93-3p和miR-105透過減少SFRP1而促進Wnt/b-catenin訊息傳遞路徑。除此之外，我們也發現到CTMP與三陰性乳癌病患的早期復發有關聯性。且過度表現CTMP可以促使三陰性乳癌病患的癌細胞轉移和抗藥性。總括而言，我們發現了miR-105/93-3p造成預後不良及它們的調控機制，以及建立了miR-105/93-3p可以當作三陰性乳癌的診斷、預測和預後的生物標誌。且對於三陰性乳癌病患來說，CTMP促使較差的臨床結果並且可能可以當作治療標的。這些結果將可以應用於三陰性乳癌的早期診斷還有個人化醫療。

Triple negative breast cancer (TNBC) lacks both early detection biomarkers and viable targeted-therapeutics. Together with the inefficiency of chemotherapeutic response and high metastatic risk, to understand the underlying mechanism of chemo-resistance and metastasis are critical issues for TNBC patients. Because miRNAs are frequently dysregulated in breast cancer and have large tissue effects, individual or combinations of circulating miRNAs may serve as ideal diagnostic, predictive or prognostic biomarkers, as well as therapeutic targets. In the current study, we identified that circulating miR-105/93-3p can serve as a diagnostic biomarker for both early and late stage TNBC by ROC curve construction (AUC= 0.928 and 0.657, respectively). miR-301b, miR-181a-3p, miR-105 and miR-93-3p were identified from 1299 patient microarray profiles with altered expression that correlated with poor survival in TNBC patients. These oncomiRs were manipulated in multiple cell lines to investigate their functional role in carcinogenesis. Among them, miR-93-3p and miR-105 promote stemness, chemoresistance and metastasis in TNBC cells. Both miR-93-3p and miR-105 were found to activate Wnt/b-catenin signaling by downregulation of SFPR1. In addition, we also found that high CTMP was correlated with early-recurrence in TNBC patients. Ectopic overexpression promoted metastasis and chemo-resistance in TNBC. In conclusion, we revealed a novel mechanism of miR105/93-3p mediated poor survival and established that circulating miR-105/93-3p can serve as a powerful diagnostic, predictive and prognostic biomarker for TNBC. Moreover, CTMP promoted unfavorable clinical outcome and may serve as a therapeutic target for TNBC patients. The results may have application in early detection and provide an optimized personalization treatment of TNBC patients.

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