<i>Retracted</i>: Gadd45a gene silencing by RNAi promotes cell proliferation and inhibits apoptosis and senescence in skin squamous cell carcinoma through the p53 signaling pathway

Liu, Liqian; Tian, Fu‐Ju; Xiong, Ying; Zhao, Yan; Song, Jianbo

doi:10.1002/jcp.26588

Cited by 14 publications

(11 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Gadd45a can also activate the JNK/P38 pathway to induce apoptosis via interaction with MEKK4/MTK1 (Takekawa and Saito, 1998). Gadd45a gene silencing inhibits apoptosis and senescence of skin squamous cell carcinoma (Liu LQ et al, 2018). In this study, Gadd45a expression has been shown to be involved in CFZ-induced apoptosis.…”

Section: Discussionmentioning

confidence: 57%

Carfilzomib inhibits the growth of lung adenocarcinoma via upregulation of Gadd45a expression

Yang

Liu

Chen

et al. 2019

J. Zhejiang Univ. Sci. B

View full text Add to dashboard Cite

Proteasome inhibitors have shown remarkable success in the treatment of hematologic neoplasm. There has been a lot of attention to applying these drugs for solid tumor treatment. Recent preclinical study has signified the effectiveness on cell proliferation inhibition in lung adenocarcinoma treated by carfilzomib (CFZ), a second generation proteasome inhibitor. However, no insight has been gained regarding the mechanism. In this study, we have systematically investigated the CFZ functions in cell proliferation and growth, cell cycle arrest, and apoptosis in lung adenocarcinoma cells. Flow cytometry experiments showed that CFZ significantly induced G2/M cell cycle arrest and apoptosis in lung adenocarcinoma. MTS and colony formation assays revealed that CFZ substantially inhibited survival of lung adenocarcinoma cells. All results were consistently correlated to the upregulation expression of Gadd45a, which is an important gene in modulating cell cycle arrest and apoptosis in response to physiologic and environmental stresses. Here, upregulation of Gadd45a expression was observed after CFZ treatment. Knocking down Gadd45a expression suppressed G2/M arrest and apoptosis in CFZ-treated cells, and reduced cytotoxicity of this drug. The protein expression analysis has further identified that the AKT/FOXO3a pathway is involved in Gadd45a upregulation after CFZ treatment. These findings unveil a novel mechanism of proteasome inhibitor in anti-solid tumor activity, and shed light on novel preferable therapeutic strategy for lung adenocarcinoma. We believe that Gadd45a expression can be a highly promising candidate predictor in evaluating the efficacy of proteasome inhibitors in solid tumor therapy.

show abstract

Section: Discussionmentioning

confidence: 57%

Carfilzomib inhibits the growth of lung adenocarcinoma via upregulation of Gadd45a expression

Yang

Liu

Chen

et al. 2019

J. Zhejiang Univ. Sci. B

View full text Add to dashboard Cite

show abstract

“…Recently, it has been reported that GADD45a silencing promotes cell proliferation and inhibits apoptosis in skin squamous cell carcinoma. Moreover, the silencing of GADD45a induced a local increased expression of cytokines such as IL-1, IL-6, TNF-α and VEGF 29 . It is conceivable that the reduction of GADD45a expression in keratinocytes from psoriasis patients could promote keratinocyte hyper-proliferation and the production of pro-inflammatory mediators.…”

Section: Discussionmentioning

confidence: 98%

Growth arrest and DNA damage-inducible proteins (GADD45) in psoriasis

Rodríguez‐Jiménez

Fernández-Messina

Ovejero‐Benito

et al. 2021

Sci Rep

View full text Add to dashboard Cite

The interplay between T cells, dendritic cells and keratinocytes is crucial for the development and maintenance of inflammation in psoriasis. GADD45 proteins mediate DNA repair in different cells including keratinocytes. In the immune system, GADD45a and GADD45b regulate the function and activation of both T lymphocytes and dendritic cells and GADD45a links DNA repair and epigenetic regulation through its demethylase activity. Here, we analyzed the expression of GADD45a and GADD45b in the skin, dendritic cells and circulating T cells in a cohort of psoriasis patients and their regulation by inflammatory signals. Thirty patients (17 male/13 female) with plaque psoriasis and 15 controls subjects (7 male/8 female), were enrolled. Psoriasis patients exhibited a lower expression of GADD45a at the epidermis but a higher expression in dermal infiltrating T cells in lesional skin. The expression of GADD45a and GADD45b was also higher in peripheral T cells from psoriasis patients, although no differences were observed in p38 activation. The expression and methylation state of the GADD45a target UCHL1 were evaluated, revealing a hypermethylation of its promoter in lesional skin compared to controls. Furthermore, reduced levels of GADD45a correlated with a lower expression UCHL1 in lesional skin. We propose that the demethylase function of GADD45a may account for its pleiotropic effects, and the complex and heterogeneous pattern of expression observed in psoriatic disease.

show abstract

“…In squamous cell carcinoma cells, knockdown of GADD45A inhibits apoptosis, with the reduction of BAX gene expression and induction of BCL-2 gene expression [48]. In addition, GADD45A methylation in DNA in serum has been suggested as a biomarker for prostate cancer in combination with PSA, since it can clinically distinguish prostate cancer [49]. Several therapeutic aids that can be used to treat prostate cancer target GADD45A [50].…”

Section: Discussionmentioning

confidence: 99%

tRNALys-Derived Fragment Alleviates Cisplatin-Induced Apoptosis in Prostate Cancer Cells

et al. 2021

View full text Add to dashboard Cite

Cisplatin is a standard treatment for prostate cancer, which is the third leading cause of cancer-related deaths among men globally. However, patients who have undergone cisplatin can rxperience relapse. tRNA-derived fragments (tRFs) are small non-coding RNAs generated via tRNA cleavage; their physiological activities are linked to the development of human diseases. Specific tRFs, including tRF-315 derived from tRNALys, are highly expressed in prostate cancer patients. However, whether tRF-315 regulates prostate cancer cell proliferation or apoptosis is unclear. Herein, we confirmed that tRF-315 expression was higher in prostate cancer cells (LNCaP, DU145, and PC3) than in normal prostate cells. tRF-315 prevented cisplatin-induced apoptosis and alleviated cisplatin-induced mitochondrial dysfunction in LNCaP and DU145 cells. Moreover, transfection of tRF-315 inhibitor increased the expression of apoptotic pathway-related proteins in LNCaP and DU145 cells. Furthermore, tRF-315 targeted the tumor suppressor gene GADD45A, thus regulating the cell cycle, which was altered by cisplatin in LNCaP and DU145 cells. Thus, tRF-315 protects prostate cancer cells from mitochondrion-dependent apoptosis induced by cisplatin treatment.

show abstract

Retracted: Gadd45a gene silencing by RNAi promotes cell proliferation and inhibits apoptosis and senescence in skin squamous cell carcinoma through the p53 signaling pathway

Cited by 14 publications

References 24 publications

Carfilzomib inhibits the growth of lung adenocarcinoma via upregulation of Gadd45a expression

Carfilzomib inhibits the growth of lung adenocarcinoma via upregulation of Gadd45a expression

Growth arrest and DNA damage-inducible proteins (GADD45) in psoriasis

tRNALys-Derived Fragment Alleviates Cisplatin-Induced Apoptosis in Prostate Cancer Cells

Contact Info

Product

Resources

About