Lentivirus-mediated RASSF1A expression suppresses aggressive phenotypes of gastric cancer cells in vitro and in vivo

Zhou, Penghui; Jb, Zheng; Gb, Wei; Xl, Wang; Wang, W; Nz, Chen; Yu, Jianping; Jf, Yao; Wang, H; Sy, Lu; Xj, Sun

doi:10.1038/gt.2015.49

Cited by 10 publications

(7 citation statements)

References 32 publications

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“…In accordance with the above mentioned observations, RASSF1A is expressed in all normal tissues and at a lower level than RASSF1C [24]. Reverting RASSF1A down-regulation in cancer cell lines restores controlled growth and colony formation, as well as decreased cell migration and apoptosis [10,25,26,27,28,29,30].…”

Section: The Tumor Suppressor Rassf1amentioning

confidence: 57%

“…It is reported that internal or environmental stimuli can promote epigenetic modifications that spread as silent events [85]. For example, RASSF1A m increases during physiological or patho-physiological processes such as aging, hypoxic conditions, senescence, inflammation, and viral infection [30,75,77,91,92,93,94,95]. De novo RASSF1A m associates with different factors and conditions; folate metabolism, DNA polymorphisms, as well as choline-deficient L-amino acid-defined diet in rats [96,97].…”

Section: Mechanisms Of Rassf1a Methylation In Cancer and Agingmentioning

confidence: 99%

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Methylation Dynamics of RASSF1A and Its Impact on Cancer

Malpeli

Innamorati

Decimo

et al. 2019

Cancers

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5-methyl cytosine (5mC) is a key epigenetic mark entwined with gene expression and the specification of cellular phenotypes. Its distribution around gene promoters sets a barrier for transcriptional enhancers or inhibitor proteins binding to their target sequences. As a result, an additional level of regulation is added to the signals that organize the access to the chromatin and its structural components. The tumor suppressor gene RASSF1A is a microtubule-associated and multitasking scaffold protein communicating with the RAS pathway, estrogen receptor signaling, and Hippo pathway. RASSF1A action stimulates mitotic arrest, DNA repair and apoptosis, and controls the cell cycle and cell migration. De novo methylation of the RASSF1A promoter has received much attention due to its increased frequency in most cancer types. RASSF1A methylation is preceded by histones modifications and could represent an early molecular event in cell transformation. Accordingly, RASSF1A methylation is proposed as an epigenetic candidate marker in many cancer types, even though an inverse correlation of methylation and expression remains to be fully ascertained. Some findings indicate that the epigenetic abrogation of RASSF1A can promote the alternative expression of the putative oncogenic isoform RASSF1C. Understanding the complexity and significance of RASSF1A methylation is instrumental for a more accurate determination of its biological and clinical role. The review covers the molecular events implicated in RASSF1A methylation and gene silencing and provides a deeper view into the significance of the RASSF1A methylation patterns in a number of gastrointestinal cancer types.

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Section: The Tumor Suppressor Rassf1amentioning

confidence: 57%

Section: Mechanisms Of Rassf1a Methylation In Cancer and Agingmentioning

confidence: 99%

Methylation Dynamics of RASSF1A and Its Impact on Cancer

Malpeli

Innamorati

Decimo

et al. 2019

Cancers

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“…Oh et al ( 29 ) reported that RASSF1A is required for full activation of macrophage stimulating 1 (Mst1) and enhanced Mst1-mediated apoptosis in vivo . Furthermore, in a previous study, we reported that RASSF1A inhibits SGC-7901 cell invasion under hypoxic conditions, which is associated with matrix metalloproteinase-2 inhibition ( 30 ). Inactivation of RASSF1A may result from multiple mechanisms in tumorigenesis, including transcriptional silencing through promoter hypermethylation, loss of heterozygosity and chromosome deficiency ( 31 ).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑181a promotes cell proliferation and inhibits apoptosis in gastric cancer by targeting RASSF1A

Sun

et al. 2018

Oncol Rep

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MicroRNA (miR)-181a is a member of the miR-181 family that serves a key role in the pathogenesis of various cancer types. The present study aimed to investigate the interaction between miR-181a and Ras association domain family protein1 isoform A (RASSF1A), and their roles in gastric carcinogenesis. The interaction between miR-181a and RASSF1A was assessed in cell lines and cancer tissues. The direct binding of miR-181a and RASSF1A was identified using a luciferase reporting gene system. The effects of miR-181a and RASSF1A on gastric cancer cell growth, cell cycle and apoptosis were assessed with a Cell Counting Kit-8 assay and flow cytometry. The effects of miR-181a on cell division cycle 25A (CDC25A), cyclin A2, cyclin D1, p21, Bcl-2-associated X protein (Bax) and B-cell lymphoma-2 (Bcl-2) protein levels were assessed in gastric cancer cell lines. miR-181a directly interacted with the 3′-untranslated region of RASSF1A and downregulated RASSF1A protein expression. In tissues from patients with gastric cancer, the miR-181a level was significantly higher in the tumor tissues and was negatively correlated with the RASSF1A protein level. RASSF1A suppressed gastric cancer cell proliferation and G1/S transition, and promoted apoptosis; whereas miR-181a promoted cancer cell proliferation and G1/S transition, and suppressed apoptosis. RASSF1A knockdown attenuated the effects of miR-181a downregulation on cell proliferation and apoptosis. Furthermore, miR-181a upregulated CDC25A, cyclin A2 and Bcl-2, and downregulated Bax protein expression in gastric cancer cell lines. These data indicate that miR-181a promotes gastric carcinogenesis, possibly through a direct interaction with RASSF1A.

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“…To restore CDX2 expression in colon cancer cells, we constructed an expression vector carrying CDX2 under the control of the hypoxia-inducible hTERT promoter (pLVX-5HRE-hTERTp-CDX2-3FLAG). Targeted genes simultaneously can be dramatically upregulated by 5 copies of a hypoxia response element (HRE) under hypoxic conditions ( 24 , 25 ).…”

Section: Introductionmentioning

confidence: 99%

Targeted CDX2 expression inhibits aggressive phenotypes of colon cancer cells in vitro and in vivo

Zheng

He²,

et al. 2017

International Journal of Oncology

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Loss of caudal type homeobox 2 (CDX2) is associated with the development of human colorectal cancer, while human telomerase reverse transcriptase (hTERT) frequently occurs in variety of human cancers. We investigated the effects of restoration of CDX2 expression using a hypoxia-inducible hTERT promoter-driven vector (pLVX-5HRE-hTERTp-CDX2-3FLAG) on colon cancer cell viability, cell cycle distribution, apoptosis, colony formation, invasion ability and xenograft tumor growth in nude mice. CDX2 overexpression significantly inhibited viability, colony formation, and the invasion and migration ability of LoVo cells, and induced cell cycle arrest and apoptosis in vitro, especially under hypoxic culture conditions. Overexpression of CDX2 under normoxic conditions significantly suppressed the expression of TGF-β, cyclin D1, uPA, MMP-9, MMP-2, and Bcl-2, and stimulated the expression of collagen IV, laminin-1, and Bax. Overexpression of CDX2 reduced colon cancer xenograft tumor formation in nude mice which was associated with downregulation of Ki-67. In conclusion, overexpression of CDX2 using a hypoxia-inducible hTERT promoter-driven vector suppressed malignant progression of colon cancer cells in vitro and in vivo. These results suggest that pLVX-5HRE-hTERTp-CDX2-3FLAG gene therapy may be a promising novel approach to treat colon cancer.

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Lentivirus-mediated RASSF1A expression suppresses aggressive phenotypes of gastric cancer cells in vitro and in vivo

Cited by 10 publications

References 32 publications

Methylation Dynamics of RASSF1A and Its Impact on Cancer

Methylation Dynamics of RASSF1A and Its Impact on Cancer

MicroRNA‑181a promotes cell proliferation and inhibits apoptosis in gastric cancer by targeting RASSF1A

Targeted CDX2 expression inhibits aggressive phenotypes of colon cancer cells in vitro and in vivo

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