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J Exp Clin Cancer Res. 2019 Jun 13;38(1):256. doi: 10.1186/s13046-019-1260-6.

PTENP1/miR-20a/PTEN axis contributes to breast cancer progression by regulating PTEN via PI3K/AKT pathway.

Gao X1,2, Qin T1, Mao J1,3,4, Zhang J5, Fan S1, Lu Y3,4, Sun Z2, Zhang Q1, Song B1, Li L6,7.

Author information

1
Department of Pathology, Dalian Medical University, 9 Lushunnan Road Xiduan, Dalian, 116044, Liaoning Province, China.
2
Department of Pathology, the First Hospital of Dalian Medical University, Dalian, 116027, Liaoning Province, China.
3
Key Laboratory of Tumor Stem Cell Research of Liaoning Province, Dalian Medical University, Dalian, 116044, Liaoning Province, China.
4
Teaching Laboratory of Morphology, Dalian Medical University, Dalian, 116044, Liaoning Province, China.
5
Teaching Affairs Department, Dalian Medical University, Dalian, 116044, Liaoning Province, China.
6
Department of Pathology, Dalian Medical University, 9 Lushunnan Road Xiduan, Dalian, 116044, Liaoning Province, China. lilianhong917@sina.com.
7
Key Laboratory of Tumor Stem Cell Research of Liaoning Province, Dalian Medical University, Dalian, 116044, Liaoning Province, China. lilianhong917@sina.com.

Abstract

BACKGROUND:

Long non-coding RNA PTENP1, the pseudogene of PTEN tumor suppressor, has been reported to exert its tumor suppressive function via modulation of PTEN expression in many malignancies, including breast cancer (BC). However, whether the PTENP1/miR-20a/PTEN axis exists and how it functions in BC progression remains elusive.

METHODS:

The levels of PTENP1, PTEN and miR-20a were measured by qRT-PCR. Furthermore, the breast cancer cells proliferation was further measured by CCK8 assay, colony formation assays, EDU and Ki67 staining. The migratory and invasive ability was determined by transwell assay. Flow cytometry, JC-1 and TUNEL assays were conducted to show the occurrence of apoptosis. Xenograft model was used to show the tumorigenesis of breast cancer cells.

RESULTS:

We analyzed PTENP1 and PTEN levels in clinical BC samples and cell lines, and found that PTENP1 and PTEN were confirmed and closely correlated with the malignancy of BC cell lines and poor clinical prognosis. Moreover, alteration of PTENP1 affects BC cell proliferation, invasion, tumorigenesis and chemoresistance to adriamycin (ADR). Bioinformatic analysis and dual-luciferase reporter gene assay predicted that PTENP1 was a direct target of miR-20a, which was clarified an alternative effect on BC aggressiveness phenotype. In addition, PTENP1 functioned as an endogenous sponge of miR-20a to regulate PTEN expression, which mediated BC cells proliferation, invasion and drug resistance via activation the phosphatidylinositol-3 kinase (PI3K)/AKT pathway. PI3K inhibitor LY294002 or siAkt also prevented BC cells progression.

CONCLUSION:

Collectively, these data indicated that PTENP1/miR-20a/PTEN axis involved in the malignant behaviors of BC cells, illuminating the possible mechanism mediated by PTEN via PI3K/Akt pathway. Targeting PTENP1/miR-20a/PTEN may provide a potential diagnosis and treatment strategy for BC.

KEYWORDS:

Breast cancer; PI3K/AKT pathway; PTEN; PTENP1; miR-20a

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