Morgana acts as a proto‐oncogene through inhibition of a <scp>ROCK–PTEN</scp> pathway

Fusella, Federica; Ferretti, Roberta; Recupero, Daniele; Rocca, Stefania; Savino, Augusta Di; Tornillo, Giusy; Silengo, Lorenzo; Turco, Emilia; Cabodi, Sara; Provero, Paolo; Pandolfi, Pier Paolo; Sapino, Anna; Tarone, Guido; Brancaccio, Mara

doi:10.1002/path.4341

Cited by 18 publications

(34 citation statements)

References 34 publications

(59 reference statements)

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“…Here we show that morgana, a chaperone protein [31][32][33][34][35] regulating ROCK activity, 8,10,14 is a tumor-suppressor gene involved in myeloid leukemogenesis. In particular, morgana 1/-mice spontaneously develop a fatal Ph-negative CML-like myeloproliferative disease.…”

Section: Discussionmentioning

confidence: 79%

“…8, 14 Morgana expression level was defined as low when staining intensity was lower compared with normal BM, specifically in the myeloid progenitor cells. Slides were scored independently by 2 pathologists.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…Western blot analysis was performed as described 14 with the indicated antibodies (see supplemental Methods).…”

Section: Western Blot Analysismentioning

confidence: 99%

“…Morgana knockdown was performed by infecting K562 cells with pGIPZ lentiviral particles expressing turboGFP and 2 different shRNAs targeting morgana (Open Biosystems). 14 …”

Section: Cell Lines and Morgana Silencingmentioning

confidence: 99%

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Morgana acts as an oncosuppressor in chronic myeloid leukemia

Savino¹,

Panuzzo

Rocca³

et al. 2015

Blood

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Section: Discussionmentioning

confidence: 79%

Section: Immunohistochemistrymentioning

confidence: 99%

“…Western blot analysis was performed as described 14 with the indicated antibodies (see supplemental Methods).…”

Section: Western Blot Analysismentioning

confidence: 99%

“…Morgana knockdown was performed by infecting K562 cells with pGIPZ lentiviral particles expressing turboGFP and 2 different shRNAs targeting morgana (Open Biosystems). 14 …”

Section: Cell Lines and Morgana Silencingmentioning

confidence: 99%

See 2 more Smart Citations

Morgana acts as an oncosuppressor in chronic myeloid leukemia

Savino¹,

Panuzzo

Rocca³

et al. 2015

Blood

Self Cite

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“…Moreover, activation of RhoA by the downstream effector Rock (RhoA-associated kinase) can stimulate the phospholipid phosphatase activity of PTEN in human embryonic kidney cells and leukocytes [31], and in turn, the activated PTEN down-regulates AKT activity, which is essential for cell proliferation [32]. Furthermore, F. Fusella, et al [33] also reported that PTEN destabilization caused by the high morgana levels in breast cancer cells triggered the PI3K/AKT survival pathway; thus, the cells' self-protective activity from various apoptotic stimuli was strongly enhanced. Differences in the apoptotic rates among different cancer cell lines caused by RhoA inhibition may be correlated with the RhoA-ROCK-PTEN pathway, but the mechanism needs to be further investigated.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of RhoA expression by adenovirus-mediated siRNA combined with TNF-α induced apoptosis of hepatocarcinoma cells

Yin

Zhao

Huang

et al. 2015

BME

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Abstract. Tumor necrosis factor-alpha (TNF-α) has been used as an effective treatment for Hepatocellular Carcinoma, however, inducing tumor cell apoptosis by TNF-α alone is still unsatisfactory. RhoA is highly expressed in hepatocarcinoma cells and can be activated by TNF-α. The activation of RhoA directly leads to a poor prognosis of HCC. Therefore, we propose to investigate the therapeutic effect of TNF-α together with RhoA siRNA. RhoA inhibition was accomplished by constructing a recombinant adenovirus that can efficiently express RhoA siRNA in HepG2 cells. The recombinant adenovirus AdshRNA-RhoA and AdU6-control were generated by adenovirus-mediated siRNA expression system. The inhibition effects were detected by RT-PCR in addition to immunoblot to quantify the decreased levels of RhoA expression, and the therapeutic effect for HCC was demonstrated by the proliferation and apoptosis ratios of HepG2 cells. The inhibition effects of RhoA by AdshRNA-RhoA were significant at both mRNA and protein levels: the transcription of RhoA mRNA decreased by 74.46%, and the expression of protein decreased by 76.48%. The proliferation rate of HepG2 cells detected by MTT showed that a treatment of AdshRNA-RhoA and TNF-α together could strengthen the suppression ability of TNF-α to HepG2 cells, resulting in approximately 14.2% more than those treated with only TNF-α. FCA and TUNEL assays results revealed that the combined treatment can induce apoptosis in approximately 52.14%-65% of the HepG2 cells, whereas this ratio in the TNF-α-alone group was only 21.91%-32%. Our results showed that AdshRNA-RhoA can efficiently enhance the TNF-α-induced apoptosis of hepatocarcinoma cells. This method might be a useful therapeutic route in HCC and other tumors.

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RETRACTED: Upregulated expression of ROCK1 promotes cell proliferation by functioning as a target of miR‐335‐5p in non‐small cell lung cancer

Tang

Jiang

et al. 2019

Journal Cellular Physiology

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Lung cancer is regarded as one of the dominant causes in cancer patients among men and women all over the world. Rho‐associated coiled‐coil forming protein kinase l (ROCK1) is characterized as pivotal downstream effectors of the small GTPase RhoA and reported to participate in tumor metastasis. miR‐335‐5p acts as tumor suppressor microRNA and is identified to be downregulated in tumor tissues. miR‐335‐5p/ROCK1 axis has been demonstrated to promote cell proliferation and metastasis in gastric cancer, hepatocellular carcinoma and so on. However, the role it plays in promoting cell proliferation in non‐small cell lung cancer (NSCLC) is poorly understood. Here, we demonstrated that the upregulated expression of ROCK1 was highly correlated with downregulated expression of miR‐335‐5p in NSCLC tissues and cell lines. Mechanistically, Knockdown of ROCK1 inhibited cell proliferation in vitro, accompanied by cell cycle change confirmed by flow analysis. Furthermore, miR‐335‐5p can downregulate the ROCK1 expression by directly binding to the 3′‐untranslated region in posttranscriptional level. In vivo animal model showed similar results. Our findings highlighted the crucial role that miR‐335‐5p acted as a tumor suppressor to modulate cell proliferation and cell cycle progression via downregulating ROCK1 expression. And this miR‐335‐5p/ROCK1 axis contributed to NSCLC pathogenesis and might be promising targets for NSCLC therapy.

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Morgana acts as a proto‐oncogene through inhibition of a ROCK–PTEN pathway

Cited by 18 publications

References 34 publications

Morgana acts as an oncosuppressor in chronic myeloid leukemia

Morgana acts as an oncosuppressor in chronic myeloid leukemia

Inhibition of RhoA expression by adenovirus-mediated siRNA combined with TNF-α induced apoptosis of hepatocarcinoma cells

RETRACTED: Upregulated expression of ROCK1 promotes cell proliferation by functioning as a target of miR‐335‐5p in non‐small cell lung cancer

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