The p21-activated kinase 4-Slug transcription factor axis promotes epithelial−mesenchymal transition and worsens prognosis in prostate cancer

Park, Jung-Jin; Park, Mee-Hee; Oh, Eui Geum; Soung, Nak-Kyun; Lee, Soo Jae; Jung, Jae‐Kyung; Lee, Ok-Jun; Yun, Seok Joong; Kim, Wun-Jae; Shin, Eun‐Young

doi:10.1038/s41388-018-0327-8

Cited by 42 publications

(34 citation statements)

References 50 publications

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“…A number of recent studies have reported on the progression of PCa and EMT in TGF-β1 regulating PCa cells (43)(44)(45)(46). However, in the present study, we found that the auto-regulatory axis miR-20b-5p/TGFBR2/E2F1, which is regulated by TGF-β1, is involved in PCa development and progression through regulating EMTrelated gene expression.…”

Section: Discussioncontrasting

confidence: 73%

miR-20b-5p, TGFBR2, and E2F1 Form a Regulatory Loop to Participate in Epithelial to Mesenchymal Transition in Prostate Cancer

Yang

Zhang

et al. 2020

Front. Oncol.

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The transcription factor E2F1 regulates the expression of the miR-20b-5p precursor and is involved in epithelial-to-mesenchymal transition (EMT). Transforming growth factor-β1 (TGF-β1) induces EMT in prostate cancer (PCa) by binding to TGF-beta receptor 2 (TGFBR2) to activate TGF-β signaling. However, the relationship between TGFBR2, E2F1, and miR-20b-5p in the modulation of EMT in PCa cells remains unknown. In this study, we found that the level of miR-20b-5p expression was significantly lower in PC3 and DU145 cells than that in prostate epithelial (RWPE-1) cells, and TGF-β1 treatment further down-regulated miR-20b-5p expression in these two cell lines. Functional studies showed that miR-20b-5p suppressed TGF-β1-induced migration and invasion of PC3 and DU145 cells by up-regulating E-cadherin and down-regulating vimentin, leading to TGF-β1-induced inhibition of EMT. Using gain and loss of function experiments, it was shown that E2F1 mediated TGF-β1 regulation of miR-20b-5p expression. Further, a luciferase activity assay showed that TGFBR2 was a direct target of miR-20b-5p in PCa cells. These results suggest that miR-20b-5p, TGFBR2, and E2F1 form a regulatory loop to modulate EMT induced by TGF-β1. A novel regulatory mechanism underlying the miR-20b-5p/TGFBR2/E2F1 axis is involved in TGF-β1-induced EMT of PCa cells, and miR-20b-5p may be a potential therapeutic target for PCa.

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Section: Discussioncontrasting

confidence: 73%

miR-20b-5p, TGFBR2, and E2F1 Form a Regulatory Loop to Participate in Epithelial to Mesenchymal Transition in Prostate Cancer

Yang

Zhang

et al. 2020

Front. Oncol.

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“…However, the underlying mechanism of the Linc01234/miR-433-3p axis in OSCC remains unclear. p21-Activated kinase 4 (PAK4), a member of the PAK family, regulates a wide range of cellular functions, including cell adhesion, migration, proliferation, and survival [26,27]. Previous studies have reported that dysregulation of PAK4 expression contributes to the development and progression of various tumors [28,29].…”

Section: Discussionmentioning

confidence: 99%

Linc01234 promotes cell proliferation and metastasis in oral squamous cell carcinoma via miR-433/PAK4 axis

Liu

Jian

et al. 2020

BMC Cancer

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Background: Increasing studies have demonstrated that long non-coding RNAs (lncRNAs) play an important role in tumor progression. However, the potential biological functions and clinical importance of Linc01234 in oral squamous cell carcinoma (OSCC) remain unclear. Methods: We evaluated the expression profile and prognostic value of Linc01234 in OSCC tissues by RT-qPCR. Then, functional in vitro experiments were performed to investigate the effects of Linc01234 on tumor growth, migration and invasion in OSCC. Mechanistically, RT-qPCR, bioinformatic analysis and dual luciferase reporter assays were performed to identify a competitive endogenous RNA (ceRNA) mechanism involving Linc01234, miR-433-3p and PAK4. Results: We found that Linc01234 was clearly upregulated in OSCC tissues and cell lines, and its level was positively associated with T stage, lymph node metastasis, differentiation and poor prognosis of patients with OSCC. Our results shown that Linc01234 inhibited cell proliferation and metastatic abilities in CAL27 and SCC25 cells following its knockdown. Mechanistic analysis indicated that Linc01234 may act as a ceRNA (competing endogenous RNA) of miR-433-3p to relieve the repressive effect of miR-433-3p on its target PAK4. Conclusions:Our results indicated that Linc01234 promotes OSCC progression through the Linc01234/miR-433/ PAK4 axis and might be a potential therapeutic target for OSCC.

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“…P21was an inhibitor of the cyclin-dependent kinase and could inhibit the activation of CDK1, CDK2, and CDK4. TK1 might interact with P21 by combining with the C-terminal domain of P21, and promote the proliferation of cancer cells (21). In addition, growth and differentiation factor 15 was considered to be the main downstream mediator of TK1 function, which induced the metastatic attributes of lung cancer cells (22).…”

Section: Discussionmentioning

confidence: 99%

Knockdown of Thymidine Kinase 1 Suppresses Cell Proliferation, Invasion, Migration, and Epithelial–Mesenchymal Transition in Thyroid Carcinoma Cells

et al. 2020

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Patients with advanced thyroid carcinoma have poor prognosis with low overall survival. Unfortunately, the underlying mechanisms of thyroid carcinoma progression remain unclear. The elevated expression of thymidine kinase 1 (TK1) has been implicated in the progression of thyroid carcinoma, while the role of TK1 in thyroid carcinoma progression has not been explored. The present study aimed to determine the role TK1 in the progression of thyroid cancer and to explore the underlying molecular mechanisms. In this study, it was found that serum TK1 levels were markedly increased in the patients with thyroid nodules. Further online data mining showed that TK1 expression was upregulated in thyroid carcinoma tissues, and higher expression of TK1 was correlated with shorter disease-free survival of patients with thyroid carcinoma. Silencing of TK1 suppressed cell proliferation, invasion, migration, and epithelial-mesenchymal transition, and also induced cell apoptosis in the thyroid carcinoma cell lines. Animal studies showed that TK1 knockdown inhibited in vivo tumor growth of thyroid carcinoma cells. Importantly, miR-34a-5p was found to be downregulated in the thyroid carcinoma cells. Furthermore, miR-34a-5p targeted the 3 ′ untranslated region of TK1 and suppressed the expression of TK1 in thyroid carcinoma cell lines. In summary, first, these results demonstrated the upregulation of TK1 in thyroid nodules and thyroid carcinoma tissues; second, TK1 promoted thyroid carcinoma cell proliferation, invasion, and migration; lastly, TK1 was negatively regulated by miR-34a-5p. Our study may provide novel insights into the role of TK1 in regulating thyroid carcinoma progression.

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The p21-activated kinase 4-Slug transcription factor axis promotes epithelial−mesenchymal transition and worsens prognosis in prostate cancer

Cited by 42 publications

References 50 publications

miR-20b-5p, TGFBR2, and E2F1 Form a Regulatory Loop to Participate in Epithelial to Mesenchymal Transition in Prostate Cancer

miR-20b-5p, TGFBR2, and E2F1 Form a Regulatory Loop to Participate in Epithelial to Mesenchymal Transition in Prostate Cancer

Linc01234 promotes cell proliferation and metastasis in oral squamous cell carcinoma via miR-433/PAK4 axis

Knockdown of Thymidine Kinase 1 Suppresses Cell Proliferation, Invasion, Migration, and Epithelial–Mesenchymal Transition in Thyroid Carcinoma Cells

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