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NKX2-2 Suppresses Osteosarcoma Metastasis and Proliferation by Downregulating Multiple Target Genes.

ABSTRACT: Osteosarcoma is the most common primary malignant bone tumor. However, our understanding of the molecular mechanism underlying its pathogenesis is incomplete. Studies have shown that aberrant expression of NK homeobox (NKX) genes may be involved in the oncogenesis of various cancers. Here, through migration screening assay, we found that a series of NKX genes inhibit the migration of osteosarcoma cells. Among these genes, NKX2-2 is a bona fide tumor suppressor for osteosarcoma. Overexpression of NKX2-2 decreases the migration, invasion, proliferation and colony formation of osteosarcoma cells in vitro and suppresses tumor growth and metastasis in vivo. Moreover, based on the results from both in vitro and in vivo studies, the transcriptional activation domain of NKX2-2 is important for its tumor suppressor function. Mechanistically, we revealed that NKX2-2 acts as a tumor suppressor partially by mediating the transcriptional downregulation of COL5A2, PLAU, SEMA7A and S1PR1 genes. In summary, our studies of NKX2-2 revealed new molecular mechanisms underlying osteosarcoma proliferation and metastasis and may provide a series of potential therapeutic targets for osteosarcoma.

SUBMITTER: Chen H

PROVIDER: S-EPMC6134811 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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NKX2-2 Suppresses Osteosarcoma Metastasis and Proliferation by Downregulating Multiple Target Genes.

Chen Huiming H Liu Wenqiang W Zhong Li L Liao Dan D Zhang Ruhua R Kang Tiebang T Wu Yuanzhong Y

Journal of Cancer 20180806 17

Osteosarcoma is the most common primary malignant bone tumor. However, our understanding of the molecular mechanism underlying its pathogenesis is incomplete. Studies have shown that aberrant expression of NK homeobox (NKX) genes may be involved in the oncogenesis of various cancers. Here, through migration screening assay, we found that a series of NKX genes inhibit the migration of osteosarcoma cells. Among these genes, NKX2-2 is a bona fide tumor suppressor for osteosarcoma. Overexpression of ...[more]

PMID: 30210629

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Project description:PURPOSE:Triple-negative breast cancer is characterized by fast progression with high possible for metastasis and poor survival. Dysfunction of microRNAs plays an important role in the initiation and progression of cancer. Our previous microRNA-seq data indicated the downregulation of miR-331-3p in triple-negative breast cancer tissues compared with that of the noncancer tissues. However, the function of miR-331-3p in triple-negative breast cancer remains largely unknown. Herein, the involvement of miR-331-3p in triple-negative breast cancer was investigated and the therapeutic potential of miR-331-3p was also explored. METHODS:Real-time quantitative polymerase chain reaction was performed to detect the expression of miR-331-3p in triple-negative breast cancer tissues and cell lines. The cell proliferation was determined by the cell counting kit-8 assay. Apoptosis of triple-negative breast cancer cells was examined by annexin V/propidium iodide staining. miRDB database was used to predict the potential targets of miR-331-3p. Western blot was performed to examine the expression of the target protein. RESULTS:miR-331-3p was significantly downregulated in triple-negative breast cancer tissues and cell line. Lower miR-331-3p expression was significantly correlated with the tumor size, TNM stage, and lymph node metastasis of patients with triple-negative breast cancer. Functional experiments showed that the overexpression of miR-331-3p inhibited the proliferation and increased apoptosis of triple-negative breast cancer cells. Neuropilin-2 was identified as a target of miR-331-3p, which harbored binding site of miR-331-3p in its 3'-untranslated region. Overexpression of miR-331-3p decreased the messenger RNA and protein levels of neuropilin-2 in triple-negative breast cancer cells. Restoration of neuropilin-2 partially reversed the inhibitory effects of miR-331-3p on the proliferation of triple-negative breast cancer cells. CONCLUSIONS:Our results demonstrated the novel function of miR-331-3p/neuropilin-2 signaling in regulating the malignant behaviors of triple-negative breast cancer cells, which suggested miR-331-3p as a potential target for the treatment of triple-negative breast cancer.

Dataset Information

NKX2-2 Suppresses Osteosarcoma Metastasis and Proliferation by Downregulating Multiple Target Genes.

Publications

NKX2-2 Suppresses Osteosarcoma Metastasis and Proliferation by Downregulating Multiple Target Genes.

Similar Datasets

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