Abstract
Breast cancer is one of the most common life-threatening cancers, mainly because of its aggressiveness and metastasis. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) participate in the development and progression of breast cancer. Nevertheless, the function and expression level of lncRNAs in breast cancer are still not fully understood. Here, we demonstrated that lncRNA PCDHB17P was up-expressed in human breast cancer tissues and cell lines. Knockdown of PCDHB17P remarkably suppressed migration and invasion, as well as tube formation ability of breast cancer cells. MiR-145-3p was significantly decreased in breast cancer samples, which was negatively correlated to the expression of PCDHB17P. In addition, we identified that MELK was a direct target gene of miR-145-3p, which was higher expressed in breast cancer tissues than that in adjacent normal tissues. Mechanistic investigation indicated that PCDHB17P acted as a cancer-promoting competing endogenous RNA (ceRNA) by binding miR-145-3p and upregulating MELK. Interestingly, MELK could in turn increase the promoter activity and expression of PCDHB17P via NF-κB, thus forming a positive feedback loop that drives the metastasis and angiogenesis of breast cancer. Overall, the results demonstrated that the constitutive activation of PCDHB17P/miR-145-3p/MELK/NF-κB feedback loop promotes the metastasis and angiogenesis of breast cancer, suggesting that this lncRNA might be a promising prognostic biomarker and therapeutic target for breast cancer.
Highlights
According to global cancer statistics in 2018, breast cancer is the second commonly diagnosed cancer (11.6% of the total cases), and ranks one of the most commonly diagnosed cancers and the primary cause of cancer-related death in females worldwide [1]
Our study revealed a PCDHB17P/miR-145-3p/maternal embryonic leucine zipper kinase (MELK)/NF-kB feedback loop network in breast cancer metastasis and angiogenesis, which gives new insights into how PCDHB17P facilitates the development of breast cancer and might provide new targets for breast cancer treatment
Metastasis and angiogenesis are typical characteristics of breast cancer, which lead to poor prognosis, frequent recurrence, and pronounced invasiveness [17]
Summary
According to global cancer statistics in 2018, breast cancer is the second commonly diagnosed cancer (11.6% of the total cases), and ranks one of the most commonly diagnosed cancers and the primary cause of cancer-related death in females worldwide [1]. Despite advances in diagnosis and treatment, the 5-year survival rate for patients with advanced breast cancer is still low [2, 3]. Mechanisms that investigate into promising molecular biomarkers that could predict the risk of metastasis, and angiogenesis of breast cancer are still in its infancy. Studies have shown that tumor angiogenesis activates the proliferation, invasion, and metastasis of cancer cells, playing an important role in the initiation and development of solid tumors, including breast cancer [5, 6]. It is well known that the more pathological angiogenesis occurs, the more cancer cells could migrate into the circulatory system and achieve distant metastasis [7]. Inhibiting angiogenesis might be an attractive strategy for cancer therapy, which is of great importance in clinic treatment of breast cancer
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