DIAPH3 promotes the tumorigenesis of lung adenocarcinoma

Guo, Xiang; He, Weiwei; Gao, Erji; Ma, Hu

doi:10.1016/j.yexcr.2019.111662

Cited by 13 publications

(23 citation statements)

References 18 publications

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“…5F-5G). DIAPH3 has been reported to promotes the expression of ERK and mesenchymal markers of EMT (34,35). We speculated RNF216 regulate the expression of these molecules through its target protein DIAPH3.…”

Section: Rnf216 Suppresses Emt and Erk By Targeting Diaph3 For Proteamentioning

confidence: 92%

“…We also found that DIAPH3, as a substrate of RNF216, also plays a central role in promoting the growth and metastasis of cholangiocarcinoma. Although DIAPH3 has been reported to be involved in the growth and metastasis of a variety of tumors (34,35,(39)(40)(41), its role in cholangiocarcinoma is not explicit. We elaborated the regulatory upstream of DIAPH3.…”

Section: Dicussionmentioning

confidence: 99%

“…DIAPH3 has been reported to be up-regulated in a variety of tumors, promoting tumor growth and metastasis (34,35,40,50). Moreover, DIAPH3 knockout in breast and prostate cancer increase the sensitivity of tumor cells to paclitaxel (29).…”

Section: Dicussionmentioning

confidence: 99%

“…DIAPH3 interacted with microtubules, and its de ciency altered microtubules dynamics, decreasing polarized force generation, contractility, and response to substrate stiffness (28)(29)(30). DIAPH3 has been reported to be upregulated in a variety of tumors, including lung cancer, liver cancer, prostatic cancer and breast cancer (31)(32)(33)(34)(35). The function of Mammalian DIAPH3 involve in assembly of actin cytoskeleton that underlies tumor cell migration and invasion (32).…”

Section: Introductionmentioning

confidence: 99%

“…The function of Mammalian DIAPH3 involve in assembly of actin cytoskeleton that underlies tumor cell migration and invasion (32). Moreover, DIAPH3 promotes the tumorigenesis of lung adenocarcinoma by interacting with STK38 thus activating ERK signaling (34). DIAPH3 was identi ed as binding protein of HSP90, which activates the beta-catenin/TCF signaling and disrupts the interaction between GSK3beta and HSP90 (35).…”

Section: Introductionmentioning

confidence: 99%

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RNF216 Promotes Occurrence and Progression of Cholangiocarcinoma via Regulation of the DIAPH3 Ubiquitination

Chen

Meng

et al. 2020

Preprint

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BackgroundCholangiocarcinoma is a relatively uncommon malignant tumor with high mortality. However, the molecular underpinnings behind malignant progression of cholangiocarcinoma are incompletely understood. Here we demonstrate that RNF216 plays a suppressive role in cholangiocarcinoma occurrence and metastasis.MethodsIHC and Western blot analysis were performed to examine the expression pattern of RNF216 and DIAPH3 in the clinical CRC cholangiocarcinoma. The relationship between RNF216 and DIAPH3 was then validated using in western blot analysis. The mechanism of RNF216-mediated ubiquitination modification of DIAPH3 was analyzed via Co-IP analysis. Gain- or loss-of-function approaches were manipulated to evaluate the modulatory effects of RNF216 and DIAPH3 on cell growth and metastasis. The mediatory effects of RNF216 and DIAPH3 on cancerogenesis were validated in vivo.ResultsClinical data indicated that expression levels of RNF216 were associated with favorable clinical outcomes. RNF216 was downregulated in cholangiocarcinoma and inhibited cell proliferation and colony formation in vitro and xenograft tumorigenicity in vivo. Moreover, RNF216 suppressed Invasion and migration of cholangiocarcinoma. Mechanistic investigations further showed that RNF216 was involved in the ubiquitination of DIAPH3, a member of formin family related to assembly of actin cytoskeleton. RNF216 elicits tumor suppressor role by promoting degradation of DIAPH3. Importantly, expression of DIAPH3 rescued RNF216-mediated suppression of proliferation, cell migration, and invasion. ConclusionOur findings uncover a suppressive role for RNF216 in cholangiocarcinoma proliferation and metastatic progression and provide novel insight into that RNF216 is a potential biomarker or serves as a therapeutic target for cholangiocarcinoma.

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Section: Rnf216 Suppresses Emt and Erk By Targeting Diaph3 For Proteamentioning

confidence: 92%

Section: Dicussionmentioning

confidence: 99%

Section: Dicussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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RNF216 Promotes Occurrence and Progression of Cholangiocarcinoma via Regulation of the DIAPH3 Ubiquitination

Chen

Meng

et al. 2020

Preprint

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Diaphanous related formin 3 knockdown suppresses cell proliferation and metastasis of osteosarcoma cells

et al. 2021

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Osteosarcoma is a malignant osteoblastic tumor that can gravely endanger the lives and health of children and adolescents. Therefore, there is an urgent need to explore new biomarkers for osteosarcoma and determine new targeted therapies to improve the efficacy of osteosarcoma treatment. Diaphanous related formin 3 (DIAPH3) promotes tumorigenesis in hepatocellular carcinoma and lung adenocarcinoma, suggesting that DIAPH3 may be a target for tumor therapy. To date, there have been no reports on the function of DIAPH3 in osteosarcoma. DIAPH3 protein expression in osteosarcoma tissues and healthy bone tissues adjacent to cancer cells was examined by immunohistochemical staining. DIAPH3 mRNA expression correlates with overall survival and reduced disease-free survival. DIAPH3 protein is upregulated in osteosarcoma tissues, and its expression is significantly associated with tumor size, tumor stage, node metastasis, and distant metastasis. Functional in vitro experiments revealed that DIAPH3 knockdown suppressed cell proliferation and suppressed cell migration and invasion of osteosarcoma cell lines MG-63 and HOS. Functional experiments demonstrated that DIAPH3 knockdown inhibited subcutaneous tumor growth and lung metastasis in vivo. In conclusion, DIAPH3 expression can predict the clinical outcome of osteosarcoma. In addition, DIAPH3 is involved in the proliferation and metastasis of osteosarcoma, and as such, DIAPH3 may be a potential therapeutic target for osteosarcoma.

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KIF20B and MET, hub genes of DIAPHs, predict poor prognosis and promote pancreatic cancer progression

Cao,

Guan,

Cheng

et al. 2024

Pathology - Research and Practice

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DIAPH3 promotes the tumorigenesis of lung adenocarcinoma

Cited by 13 publications

References 18 publications

RNF216 Promotes Occurrence and Progression of Cholangiocarcinoma via Regulation of the DIAPH3 Ubiquitination

RNF216 Promotes Occurrence and Progression of Cholangiocarcinoma via Regulation of the DIAPH3 Ubiquitination

Diaphanous related formin 3 knockdown suppresses cell proliferation and metastasis of osteosarcoma cells

KIF20B and MET, hub genes of DIAPHs, predict poor prognosis and promote pancreatic cancer progression

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