Original articleLncRNA MEG3 inhibits cell epithelial-mesenchymal transition by sponging miR-421 targeting E-cadherin in breast cancer
Introduction
Breast cancer is one of the most common cancers worldwide. In 2015, approximately 231,840 new cases of invasive breast cancer and 40,290 breast cancer deaths are occurred in USA [1]. In clinic, signaling by estrogen receptor (ER), progesterone receptor (PR), and/or human EGF-like receptor 2 (HER2) is an important driver in the development and progression of a large majority of breast tumors [2], [3]. Despite the advances of diagnosis and treatment including radical surgery and adjuvant therapy, the over survival rate for advanced stage patients remains poor due to the aggressive clinical behavior [4], [5]. Thus, investigating novel target of breast cancer treatment is urgently important.
Long non-coding RNAs (lncRNAs) are a novel class of RNA transcripts more than 200 nucleotides in length without protein-coding capacity [6]. Recent studies have shown that lncRNAs exert critically roles in various biological processes and are found to be dysregulated in some diseases including tumors [7]. Long non-coding RNA MEG3 (lncRNA MEG3) functions as tumor suppressors to be involved in a variety of cancers progression [8]. Such as, decreased expression of long non-coding RNA MEG3 acts as a potential predictor biomarker in progression and poor prognosis of osteosarcoma [9]. Long non-coding RNA MEG3 inhibits NSCLC cells proliferation and induces cell apoptosis by affecting p53 expression [10]. Down-regulation of long non-coding RNA MEG3 is associated with poor prognosis and promoter hypermethylation in cervical cancer [11]. LncRNA-MEG3 inhibits cell proliferation of endometrial carcinoma by repressing Notch signaling pathway [12]. In breast cancer development and progression, lower long non-coding RNA MEG3 serves as an unfavorable risk factor for survival of patients with breast cancer [13]. Down-regulated long non-coding RNA MEG3 in breast cancer inhibits cell proliferation, migration and invasion by depending on p53's transcriptional activity [14].
In the study, we demonstrated that the expression of MEG3 was significantly lower expression and up-regulated MEG3 inhibited cell proliferation and cell invasion ability. Meanwhile, MEG3 inhibited cell epithelial-mesenchymal transition (EMT) by regulating E-cadherin expression sponging to miR-421 in breast cancer. Thus, our results showed that MEG3/miR-421/E-cadherin regulatory axis may be a novel therapeutic target for breast cancer.
Section snippets
Breast cancer tissue samples
Human primary breast cancer and their matched normal adjacent tissues were obtained from 90 cases of patients who received radical surgery at Breast Surgery, Ningbo NO.2 Hospital from July 2010 to Feb 2015. The diagnosis was based on pathological confirmation. None of the patients had received preoperative radiotherapy, chemotherapy or any other medical intervention. Tumors were staged according to the Seventh Edition of the Cancer Staging Manual by the American Joint Committee on Cancer. The
MEG3 is down-regulated in breast cancer tissues and cells
To explore the role of MEG3 in breast cancer, we performed the qRT-PCR assays. The results of qRT-PCR analysis demonstrated that the expression of MEG3 was significantly lower in breast cancer tissues compared to corresponding normal tissues(Fig. 1A, P < 0.05). To further assessed the relationship between MEG3 level and clinicopathological factors of breast cancer, we found that lower MEG3 expression was associated with lymph node metastasis and TNM stage (Table 1, P < 0.05), but there was no
Discussion
Recently, long noncoding RNAs (lncRNAs) have emerged as important regulators in governing fundamental biological processes including breast cancer, in the study, we demonstrated that the expression of MEG3 was significantly down-regulated in breast cancer tissues compared to adjacent normal tissues. Reducing MEG 3 expression was significantly associated with TNM stage and lymph nodes metastasis. In previous report, the expression of MEG3 was significantly lower in some tumors, such as, the
Ethics approval and consent to participate
Written informed consent was obtain from all patients before surgery. This study was approved by the Human Ethics Committee of Ningbo NO.2 Hospital and the study was conducted according to the principles expressed in the Declaration of Helsinki.
Consent for publication
All authors approved the final manuscript for publication.
Competing interests
None.
Authors’ contributions
Experimental concepts and design: Wei Zhang and Feng Ren.
Data acquisition and collection: Sheng-hong Shi, Jing Jiang and Xu-jun Li,
Data analysis: Xu-jun Li and Hong-feng Lu.
Manuscript writing: Wei Zhang and Feng Ren.
Funds
Not applicable.
Acknowledgment
Not applicable.
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