Adenovirus-mediated expression of spermidine/spermine N1-acetyltransferase gene induces S-phase arrest in human colorectal cancer cells

Sun, Hui; Liu, Bin; Wang, Wei; Jiang, Guang-shui; Li, Wei; Yang, Yong; Xu, Chunxiao; Yan, Yun‐Fei; Liu, Xianxi

doi:10.3892/or_00000134

Cited by 4 publications

(3 citation statements)

References 10 publications

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“…Existing research (Du et al, 2022, Duxbury, Matros, et al, 2004 as gastric cancer, osteosarcoma, prostate cancer, liver cancer, and so on. The upregulation of E2F1 expression is closely associated with the occurrence, development, metastasis, and prognosis of tumors (Liang et al, 2016;Sun et al, 2008;Wang et al, 2017;Ye et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

“…Studies have demonstrated that E2F1 is greatly expressed in diverse tumors such as gastric cancer, osteosarcoma, prostate cancer, liver cancer, and so on. The upregulation of E2F1 expression is closely associated with the occurrence, development, metastasis, and prognosis of tumors (Liang et al, 2016; Sun et al, 2008; Wang et al, 2017; Ye et al, 2021). The above results suggest that silencing GGTase‐I is capable of inhibiting the modification of RhoA protein and thus affecting RhoA protein activity, rather than inhibiting RhoA protein expression.…”

Section: Discussionmentioning

confidence: 99%

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Silencing geranylgeranyltransferase I inhibits the migration and invasion of salivary adenoid cystic carcinoma through RhoA/ROCK1/MLC signaling and suppresses proliferation through cell cycle regulation

Chi,

Wang,

Tong

et al. 2023

Cell Biology International

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Geranylgeranyltransferase type I (GGTase‐I) significantly affects Rho proteins, such that the malignant progression of several cancers may be induced. Nevertheless, the effect and underlying mechanism of GGTase‐I in the malignant progression of salivary adenoid cystic carcinoma (SACC) remain unclear. This study primarily aimed to investigate the role and mechanism of GGTase‐I in mediating the malignant progression of SACC. The level of GGTase‐I gene in cells was stably knocked down by short hairpin RNA‐EGFP‐lentivirus. The effects of GGTase‐I silencing on the migration, invasion, and spread of cells were examined, the messenger RNA levels of GGTase‐I and RhoA genes of SACC cells after GGTase‐I knockdown were determined, and the protein levels of RhoA and RhoA membrane of SACC cells were analyzed. Moreover, the potential underlying mechanism of silencing GGTase‐I on the above‐mentioned aspects in SACC cells was assessed by examining the protein expression of ROCK1, MLC, p‐MLC, E‐cadherin, Vimentin, MMP2, and MMP9. Furthermore, the underlying mechanism of SACC cells proliferation was investigated through the analysis of the expression of cyclinD1, MYC, E2F1, and p21CIP1/WAF1. Besides, the change of RhoA level in SACC tissues compared with normal paracancer tissues was demonstrated through quantitative reverse‐transcription polymerase chain reaction and western blot experiments. Next, the effect after GGTase‐I silencing was assessed through the subcutaneous tumorigenicity assay. As indicated by the result of this study, the silencing of GGTase‐I significantly reduced the malignant progression of tumors in vivo while decreasing the migration, invasion, and proliferation of SACC cells and RhoA membrane, Vimentin, ROCK1, p‐MLC, MMP2, MMP9, MYC, E2F1, and CyclinD1 expression. However, the protein expression of E‐cadherin and p21CIP1/WAF1 was notably upregulated. Subsequently, no significant transform of RhoA and MLC proteins was identified. Furthermore, RhoA expression in SACC tissues was significantly higher than that in paracancerous tissues. As revealed by the results of this study, GGTase‐I shows a correlation with the proliferation of SACC through the regulation of cell cycle and may take on vital significance in the migration and invasion of SACC by regulating RhoA/ROCK1/MLC signaling pathway. GGTase‐I is expected to serve as a novel exploration site of SACC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Silencing geranylgeranyltransferase I inhibits the migration and invasion of salivary adenoid cystic carcinoma through RhoA/ROCK1/MLC signaling and suppresses proliferation through cell cycle regulation

Chi,

Wang,

Tong

et al. 2023

Cell Biology International

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“…SSAT expressing recombinant adenovirus, Ad-SSAT was reported to cause a surge in the enzyme expression, where it limited the growth of HT-29 cells by arresting the cell cycle in S-phase. As seen from the reporter gene assay, Ad-SSAT suppressed the expression of nuclear factor E2F-1 and cyclin A in Lovo cells and HT-29 cells ( Sun et al, 2008a ).…”

Section: Spermidine/spermine N1-acetyltransferase (Ssat)-induced Anti...mentioning

confidence: 94%

Spermidine as a promising anticancer agent: Recent advances and newer insights on its molecular mechanisms

et al. 2023

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Spermidine is a naturally occurring polyamine compound found in semen. It is also found in several plant sources and boasts a remarkable biological profile, particularly with regards to its anticancer properties. Spermidine specifically interferes with the tumour cell cycle, resulting in the inhibition of tumor cell proliferation and suppression of tumor growth. Moreover, it also triggers autophagy by regulating key oncologic pathways. The increased intake of polyamines, such as spermidine, can suppress oncogenesis and slow the growth of tumors due to its role in anticancer immunosurveillance and regulation of polyamine metabolism. Spermidine/spermine N-1-acetyltransferase (SSAT) plays a critical role in polyamine homeostasis and serves as a diagnostic marker in human cancers. Chemically modified derivatives of spermidine hold great potential for prognostic, diagnostic, and therapeutic applications against various malignancies. This review discusses in detail the recent findings that support the anticancer mechanisms of spermidine and its molecular physiology.

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Spermidine/spermine N1-acetyltransferase regulates cell growth and metastasisviaAKT/β-catenin signaling pathways in hepatocellular and colorectal carcinoma cells

et al. 2016

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Hepatocellular carcinoma (HCC) and colorectal cancer (CRC) are among the most common cancers across the world. Therefore, identifying the potential molecular mechanisms that promote HCC and CRC progression and metastasis are urgently needed. Spermidine/spermine N1-acetyltransferase (SSAT) is a catabolic enzyme that acetylates the high-order polyamines spermine and spermidine, thus decreasing the cellular content of polyamines. Several publications have suggested that depletion of intracellular polyamines inhibited tumor progression and metastasis in various cancer cells. However, whether and how SSAT regulates cell growth, migration and invasion in hepatocellular and colorectal carcinoma cells remains unclear. In this study, depletion of polyamines mediated by SSAT not only attenuated the tumor cell proliferation but also dramatically inhibited cell migration and invasion in hepatocellular and colorectal carcinoma cells. Subsequent investigations revealed introduction of SSAT into HepG2, SMMC7721 hepatocellular carcinoma cells and HCT116 colorectal carcinoma cells significantly suppressed p-AKT, p-GSK3β expression as well as β-catenin nuclear translocation, while inhibition of GSK3β activity or exogenous polyamines could restore SSAT-induced decreases in the protein expression of p-AKT, p-GSK3β and β-catenin. Conversely, knockdown of SSAT in Bel7402 hepatocellular carcinoma cells and HT-29 colorectal carcinoma cells which expressed high levels of SSAT endogenously significantly promoted the expression of p-AKT, p-GSK3β as well as β-catenin nuclear translocation. Taken together, our results indicated depletion of polyamines by SSAT significantly inhibited cell proliferation, migration and invasion through AKT/GSK3β/β-catenin signaling pathway in hepatocellular carcinoma and colorectal cancer cells.

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Adenovirus-mediated expression of spermidine/spermine N1-acetyltransferase gene induces S-phase arrest in human colorectal cancer cells

Cited by 4 publications

References 10 publications

Silencing geranylgeranyltransferase I inhibits the migration and invasion of salivary adenoid cystic carcinoma through RhoA/ROCK1/MLC signaling and suppresses proliferation through cell cycle regulation

Silencing geranylgeranyltransferase I inhibits the migration and invasion of salivary adenoid cystic carcinoma through RhoA/ROCK1/MLC signaling and suppresses proliferation through cell cycle regulation

Spermidine as a promising anticancer agent: Recent advances and newer insights on its molecular mechanisms

Spermidine/spermine N1-acetyltransferase regulates cell growth and metastasisviaAKT/β-catenin signaling pathways in hepatocellular and colorectal carcinoma cells

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