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DEP Domain-Containing Protein 1B (DEPDC1B) Promotes Migration and Invasion in Pancreatic Cancer Through the Rac1/PAK1-LIMK1-Cofilin1 Signaling Pathway.

ABSTRACT: Background:With increasing incidence, pancreatic cancer (PC) is one of the most common digestive tract tumors. However, the prognosis of PC is particularly dismal due to the highly invasive and metastatic behavior of this deadly disease. DEP domain-containing protein 1B (DEPDC1B), which is overexpressed in multiple tumors, such as breast cancer, oral cancer and non-small cell lung cancer, plays a significant role in cell movement, cell cycle and cytoskeleton reorganization. However, the function of DEPDC1B in PC remains poorly understood. Methods:The function of DEPDC1B in the migration and invasion of PC was evaluated by wound healing and Transwell assays in vitro and PC-derived liver metastasis models in vivo. The molecular mechanisms of DEPDC1B were investigated through cell line establishment, Western blotting, qRT-PCR, immunoprecipitation, histological examination and immunohistochemistry analysis. Results:DEPDC1B was overexpressed in PC cell lines. DEPDC1B regulated cell migration and invasion. DEPDC1B regulated the Rac1/PAK1-LIMK1-cofilin1 signaling pathway by interacting with Rac1. Rac1 inhibition suppressed DEPDC1B-induced migration and invasion in PC in vitro and DEPDC1B-induced liver metastasis in vivo. Conclusion:DEPDC1B promoted cell migration and invasion by activating the Rac1/PAK1-LIMK1-cofilin1 signaling pathway, thus providing a potential therapeutic target against PC.

SUBMITTER: Zhang S

PROVIDER: S-EPMC7035893 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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DEP Domain-Containing Protein 1B (DEPDC1B) Promotes Migration and Invasion in Pancreatic Cancer Through the Rac1/PAK1-LIMK1-Cofilin1 Signaling Pathway.

Zhang Shan S Shi Weiwei W Hu Wei W Ma Ding D Yan Dongliang D Yu Kuanyong K Zhang Guang G Cao Yin Y Wu Junhua J Jiang Chunping C Wang Zhongxia Z

OncoTargets and therapy 20200218

<h4>Background</h4>With increasing incidence, pancreatic cancer (PC) is one of the most common digestive tract tumors. However, the prognosis of PC is particularly dismal due to the highly invasive and metastatic behavior of this deadly disease. DEP domain-containing protein 1B (DEPDC1B), which is overexpressed in multiple tumors, such as breast cancer, oral cancer and non-small cell lung cancer, plays a significant role in cell movement, cell cycle and cytoskeleton reorganization. However, the ...[more]

PMID: 32110046

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Project description:ObjectivesThis research aims to verify that the long non-coding RNA differentiation antagonizing nonprotein coding RNA (LncRNA DANCR) could modulate the proliferation and metastasis of hepatocellular carcinoma (HCC), and it thus may work as a novel biomarker to render new orientation for early diagnosis and clinical therapy of HCC.Materials and methodsFirstly, qRT-PCR was used to detect the expression of genes including LncRNA DANCR and miR-27a-3p. Next, MTT assay, Ethynyldeoxyuridine (EdU) analysis and clone formation assay were used for investigating cell growth and proliferation. Meanwhile, transwell assay and wound healing assay were applied to evaluate the capacity of cell metastasis and motility, respectively. In addition, bioinformatic analysis and dual-luciferase reporter assay were applied to analyse molecular interaction. Next, we conducted immunofluorescence and Western blot for mechanic investigation. Last but not the least, xenograft tumours in nude mice were built by subcutaneously injecting Hep3B cells stably transfected with sh-NC and sh-DANCR to detect proliferation and SMMC-7721 cells stably transfected with sh-NC and sh-DANCR to investigate metastasis.ResultsThe results of qRT-PCR and bioinformatic analysis revealed the high expression of DANCR in HCC. DANCR accelerated proliferation and metastasis of HCC cells and the knockdown of DANCR had the opposite effect. Meanwhile, xenograft tumours in sh-DANCR group grow slower and have smaller volumes compared with negative control group. Next, the antineoplastic effect of miR-27a-3p on cell growth and motility of HCC was confirmed. In addition, we clarified that DANCR acted as a ceRNA to decoy miR-27a-3p via mediating ROCK1/LIMK1/COFILIN1 pathway. In the end, we validated that DANCR/miR-27a-3p axis regulates EMT progression by cell immunofluorescence and Western blot.ConclusionsIn a word, DANCR promotes HCC development and induces EMT by decoying miR-27a-3p to regulate ROCK1/LIMK1/COFILIN1 pathway.

Dataset Information

DEP Domain-Containing Protein 1B (DEPDC1B) Promotes Migration and Invasion in Pancreatic Cancer Through the Rac1/PAK1-LIMK1-Cofilin1 Signaling Pathway.

Publications

DEP Domain-Containing Protein 1B (DEPDC1B) Promotes Migration and Invasion in Pancreatic Cancer Through the Rac1/PAK1-LIMK1-Cofilin1 Signaling Pathway.

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