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Long noncoding RNA Linc00460 promotes breast cancer progression by regulating the miR-489-5p/FGF7/AKT axis

Authors Zhu Y, Yang L, Chong QY, Yan H, Zhang W, Qian W, Tan S, Wu Z, Lobie PE, Zhu T

Received 28 February 2019

Accepted for publication 27 April 2019

Published 1 July 2019 Volume 2019:11 Pages 5983—6001


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Ahmet Emre Eskazan

Yong Zhu,1 Leiyan Yang,1 Qing-Yun Chong,2 Hong Yan,3 Weijie Zhang,1 Wenchang Qian,1 Sheng Tan,1 Zhengsheng Wu,4 Peter E Lobie,5 Tao Zhu1

1Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, People’s Republic of China; 2Cancer Science Institute of Singapore and Department of Pharmacology, National University of Singapore, Singapore, Singapore; 3Department of Pathology, Anhui Provincial Cancer Hospital, The First Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui, People’s Republic of China; 4Department of Pathology, Anhui Medical University, Hefei, Anhui 230032, People’s Republic of China; 5Tsinghua-Berkeley Shenzhen Institute, Tsinghua University, Shenzhen, Guangdong, People’s Republic of China

Purpose: Evidence indicates that long noncoding RNAs (lncRNA) possess important roles in various cellular processes and that dysregulation of lncRNAs promotes tumor progression. However, the expression patterns and biological functions of many specific lncRNAs in breast cancer remain to be determined.
Methods: Quantitative real-time polymerase chain reaction was performed to detect Linc00460, miR-489-5p and FGF7 expression. Protein levels were determined using Western blot. MTT and colony formation assay were used to measure cell proliferation. Transwell assays were conducted to determine cell migration and invasion. Luciferase reporter assays were carried out to assess the interaction between miR-489-5p and Linc00460 or FGF7. Biotin pull-down assay was used to detect the direct interaction between miR-489-5p and Linc00460. In vivo experiments were performed to measure tumor formation and lung metastasis.
Results: We demonstrated that lncRNA Linc00460 was upregulated in breast cancer, and its expression level was positively associated with lymphatic metastasis and poor overall survival. Forced expression of Linc00460 increased, whereas Linc00460 silencing decreased, breast cancer cell viability, migration and invasion both in vitro and in vivo. Linc00460 was identified as a direct target of miR-489-5p, which further targeted FGF7 and exerted oncogenic functions in breast cancer. Mechanistically, Linc00460 served as a competing endogenous RNA of FGF-7 mRNA by sponging miR-489-5p, resulting in upregulated FGF7 expression and AKT activity. Notably, forced expression of miR-489-5p abrogated Linc00460-mediated oncogenic behavior and activation of the FGF7-AKT pathway in breast cancer cells.
Conclusion: We have demonstrated that Linc00460 promotes breast cancer progression partly through the miR-489-5p/FGF7/AKT axis.

Keywords: Linc00460, miR-489-5p, breast cancer, FGF7, AKT

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