Low Expression of Circulating MicroRNA-34c is Associated with Poor Prognosis in Triple-Negative Breast Cancer

Background and Objectives: Kidney and brain protein (KIBRA) is a protein encoded by the WW and C2 domain containing 1 (WWC1) gene and is involved in the Hippo signaling pathway. Recent studies have revealed the prognostic value of KIBRA expression; however, its role in breast cancer remains unclear. The aim of this study was to examine KIBRA expression in relation to the clinical and pathological characteristics of patients with breast cancer and to disease outcomes. Materials and Methods: We analyzed the expression of KIBRA and its correlation with event-free survival (EFS) outcomes in resected samples from 486 patients with breast cancer. Results: KIBRA expression was significantly different among the molecular subgroups (low KIBRA expression: luminal A, 46.7% versus 50.0%, p = 0.641; luminal B, 32.7% versus 71.7%, p < 0.001; human epidermal growth factor receptor 2 (HER2)-enriched, 64.9% versus 45.5%. p = 0.001; triple-negative, 73.6% versus 43.8%, p < 0.001). Low KIBRA expression was also associated with high nuclear grade (60.4% versus 37.8%, p < 0.001), high histologic grade (58.7% versus 37.0%, p < 0.001), and estrogen receptor (ER) negativity (54.2% versus 23.6%, p < 0.001). Low KIBRA expression was significantly associated with poor EFS (p = 0.041; hazard ratio (HR) 1.658; 95% confidence interval (CI), 1.015–2.709). Low KIBRA expression was an independent indicator of poor prognosis (p = 0.001; HR = 3.952; 95% CI = 1.542–10.133) in triple-negative breast cancer (TNBC). Conclusion: Low KIBRA expression was associated with higher histological grade, ER negativity and poor EFS of breast cancer. In particular, our data highlight KIBRA expression status as a potential prognostic marker for TNBC.

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Expression of synuclein gamma indicates poor prognosis of triple-negative breast cancer

Medical Oncology ◽

10.1007/s12032-013-0612-x ◽

2013 ◽

Vol 30 (3) ◽

Cited By ~ 13

Author(s):

Kejin Wu ◽

Shuo Huang ◽

Mingjie Zhu ◽

Yunshu Lu ◽

Jian Chen ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Poor Prognosis ◽

Triple Negative ◽

Synuclein Gamma

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miR-9-5p Promotes β-Catenin-Activated Epithelial-To-Mesenchymal Transition of Triple-Negative Breast Cancer Via Targeting LZTS2

10.21203/rs.3.rs-105343/v1 ◽

2020 ◽

Author(s):

Jie Zhang ◽

Lina Zhang ◽

Jianlong Wang ◽

Jing Zhao ◽

Xuelian Zhao ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Suppressor ◽

Triple Negative Breast Cancer ◽

Nuclear Export ◽

Triple Negative ◽

Tumor Model ◽

Migration And Invasion ◽

Xenograft Tumor ◽

Xenograft Tumor Model ◽

Low Expression

Abstract Background: Leucine zipper tumor suppressor 2 (LZTS2), an emerging tumor-suppressor, is attenuated in multiple cancers including prostate, lung and colon cancer. However, its expression and upstream regulatory mechanisms in triple negative breast cancer (TNBC) still remain unknown.Materials and methods: The expression of LZTS2 in TNBC and matched para-carcinoma tissues was detected with immunohistochemistry. The correlations between LZTS2 expression and clinicopathological parameters were analyzed. Kaplan-Meier analysis was performed to determine the prognostic role of LZTS2 for TNBC patients. CCK-8, wound healing and transwell assay were used to detect the effect of LZTS2 overexpression on the proliferation, migration and invasion ability, respectively. The bioinformation algorithms were used to reveal the potential upstream regulatory miRNA. Then, dual-luciferase reporter assay was performed to confirm the regulatory effect of the chosen miRNA on the expression of LZTS2. miR-9-5p inhibitor was used to determine the effect of miR-9-5p on the subcellular localization of β-catenin. Then, western blotting was performed to reveal the effect of miR-9-5p on EMT-related proteins in TNBC cells. Xenograft tumor model was established to reveal the effect of miR-9-5p on TNBC progression in vivo.Results: Low expression of LZTS2 was observed in 62 of 95 cases of TNBC tissue. Low expression of LZTS2 was correlated with poor postoperative DFS and OS of TNBC patients. LZTS2 could inhibit the proliferation, migration and invasion ability of TNBC cells. LZTS2 could be downregulated by miR-9-5p in TNBC, and the nuclear export of β-catenin was suppressed. Consequently, miR-9-5p inhibitor downregulated E-cadherin and upregulated N-cadherin, Twist and Vimentin in TNBC cells. Xenograft tumor model showed that miR-9-5p inhibitor could upregulate the expression of LZTS2 and induce nuclear export of β-catenin in TNBC.Conclusions: miR-9-5p contributes to β-catenin-activated EMT via downregulating LZTS2, and thus promotes TNBC progression.

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