SCIENCE@home

Knockdown of LncRNA MAPT-AS1 inhibites proliferation and migration and sensitizes cancer cells to paclitaxel by regulating MAPT expression in ER-negative breast cancers

Yiyuan Pan,Yi-fei Pan,Yue Cheng,Fan Yang,Z. Yao,O. Wang

Published 2018 in Cell & Bioscience

ABSTRACT

MAPT-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. We 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. 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. 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. Our 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.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-35 of 35 references · Page 1 of 1

CITED BY

Showing 1-49 of 49 citing papers · Page 1 of 1