Abstract
BackgroundMAPT-AS1, a long non-coding RNA, has not been reported in any previous research about its function in cancers. In this study, we investigated the role of MAPT-AS1 in the progression and paclitaxel resistance in breast cancer, and the regulation between MAPT-AS1 and its natural comparable sense transcripts MAPT.MethodsWe analysed the breast cancer patients’ clinical information and explored the function of MAPT-AS1 by gain- and loss-of function assays in vitro and in vivo. The regulation between MAPT-AS1 and MAPT was confirmed by gene expression analysis and rescue assays. To verify the hypothesis that MAPT-AS1 and MAPT might form a duplex structure, we performed RT-PCR assays on RNA after α-amanitin treatment.ResultsBy analysing the breast cancer patients’ clinical information from the TCGA database, we found that ER-negative patients with younger age (< 60), larger tumors (≥ 2 cm), metastatic lymph nodes and stages (III–IV) had higher expression of MAPT-AS1. MAPT-AS1 is correlated with the cell growth, invasiveness and paclitaxel resistance by regulating its natural comparable sense transcripts MAPT in ER-negative breast cancer cells. The result revealed that MAPT-AS1 overexpression could partially protect the MAPT mRNA from degradation, while MAPT-AS1 knockdown decreased the stability of MAPT mRNA. Meanwhile, MAPT knockdown decreased the expression of MAPT-AS1 mRNA. MAPT-AS1 expressed coordinately with MAPT in breast tumor tissues.ConclusionOur study is the first to report a novel lncRNA MAPT-AS1 in human cancer. ER-negative patients with younger age (< 60), larger tumors (≥ 2 cm), metastatic lymph nodes and stages (III–IV) had higher expression of MAPT-AS1. MAPT-AS1 is correlated with the cell growth, invasiveness and paclitaxel resistance in ER-negative breast cancer cells through antisense pairing with MAPT. MAPT-AS1 may serve as a potential therapeutic target in ER-negative breast cancers.
Highlights
MAPT-AS1, a long non-coding RNA, has not been reported in any previous research about its function in cancers
MAPT-AS1 is an 840 bp RNA transcribed from chromosome 17, the opposite strand of MAPT (17q21.31) [16], and it consists of two exons (Fig. 1b)
By analysing the breast cancer patients’ clinical information from the TCGA database, we found that ER-negative patients with younger age (< 60), larger tumors (≥ 2 cm), metastatic lymph nodes and stages (III–IV) had higher expression of MAPT-AS1 (Fig. 1e–h)
Summary
MAPT-AS1, a long non-coding RNA, has not been reported in any previous research about its function in cancers. We investigated the role of MAPT-AS1 in the progression and paclitaxel resistance in breast cancer, and the regulation between MAPT-AS1 and its natural comparable sense transcripts MAPT. A large number of studies have identified the tumorigenic role of lncRNAs in breast cancer. Xu et al identified that lncRNAs can promote cell proliferation and metastasis; they can serve as a biomarker to diagnose and treat breast cancer in China [13]. We performed the whole-transcriptome sequencing of 23 pairs of breast cancer tumor samples and adjacent non-tumorous tissues, and MAPT-AS1 was originally identified. We performed a series of in vivo and in vitro studies to explore the role and mechanism of lncRNA MAPT-AS1 in breast cancer
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