Downregulation of Skp2 inhibits the growth and metastasis of gastric cancer cells in vitro and in vivo

Wei, Zheng; Jiang, Xian; Liu, Fengjun; Qiao, Haiquan; Zhou, Baojian; Zhai, Bo; Zhang, Lianfeng; Zhang, Xuwen; Han, Likun; Jiang, Hongchi; Krissansen, Geoffrey W.; Sun, Xueying

doi:10.1007/s13277-012-0527-8

Cited by 45 publications

(37 citation statements)

References 40 publications

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“…Skp2, S-phase kinase-associated protein 2; si, small interfering. ubiquitin-protein ligase complex which regulates the progression of the cell cycle by degrading the tumor suppressor gene p27 kip1 in a ubiquitin-mediated manner (17,18,(33)(34)(35). In the present study, the effects Skp2 depletion by RNAi on cell cycle progression in colon cancer cells were also identified.…”

Section: Discussionmentioning

confidence: 60%

Interference of Skp2 effectively inhibits the development and metastasis of colon carcinoma

Chen¹,

Mo²,

Yu³

et al. 2014

Molecular Medicine Reports

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Abstract. Colon cancer is a common type of malignancy in the digestive system. The aim of the present study was to investigate the role of S-phase kinase-associated protein 2 (Skp2) in colon carcinoma and to identify whether depletion of Skp2 by Skp2-RNA interference (RNAi) attenuates the proliferation and migration of colon carcinoma. Three pairs of small interfering (si)RNA were designed based on the Skp2 gene sequence and the most effective one was used to silence the Skp2 gene in SW620 cells. Subsequent to the interference, quantitative polymerase chain reaction and western blot analysis were used for detecting the expression of Skp-2 mRNA and protein, respectively. The data demonstrated that the Skp2-siRNA effectively inhibited proliferation (P<0.01), increased the levels of apoptosis and induced G 0 /G 1 phase arrest of the SW620 cells (P<0.01). Transfection of the Skp2 siRNA into SW620 cells effectively reduced Skp2 protein levels, while p27 protein levels increased. In the in vivo experiments, a lentiviral vector of the Skp2-RNAi transfected into SW620 cells markedly inhibited Skp2 expression, as detected by immunohistochemical analysis of nude mice. Additionally, tumorigenicity experiments showed that inhibition of Skp2 significantly increased the survival rate of nude mice. Thus, the in vitro and in vivo results demonstrated that interference of Skp2 expression significantly inhibited the proliferation and induced the apoptosis of SW620 cells. This suggests that Skp2 protein has an important role in the progression of colon cancer. Therefore, Skp2 may enable the early diagnosis of colon cancer and provide new insights into molecular targets for cancer therapy.

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Section: Discussionmentioning

confidence: 60%

Interference of Skp2 effectively inhibits the development and metastasis of colon carcinoma

Chen¹,

Mo²,

Yu³

et al. 2014

Molecular Medicine Reports

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“…Cell migration and invasion assays were performed as previously described (18). For the migration assays, 2.5x10 4 cells suspended in 500 µl serum-free RPMI-1640 medium were seeded in BD Falcon cell culture inserts (8-µm pore; BD Biosciences, San Jose, CA, USA).…”

Section: Reverse Transcription-quantitative Pcr (Rt-qpcr)mentioning

confidence: 99%

“…A gelatin zymography assay was performed as previously described (18). Cells (30.0x10 4 ) were seeded in 6-well plates and starved with serum-free medium for 24 h. The conditioned medium was collected and ultracentrifuged.…”

Section: Reverse Transcription-quantitative Pcr (Rt-qpcr)mentioning

confidence: 99%

Depletion of histone deacetylase 1 inhibits metastatic abilities of gastric cancer cells by regulating the miR-34a/CD44 pathway

et al. 2015

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Abstract. Overexpression of histone deacetylases (HDACs) is associated with higher metastatic rates and a poor prognosis in gastric cancer. However, the underlying mechanisms involved remain unclear. The present study aimed to investigate the molecular pathways that are involved in HDAC1-mediated metastatic activities in gastric cancer cells. First we used a microRNA (miRNA or miR) microarray to screen potential miRNAs whose expression can be altered by HDAC1 depletion. Of these miRNAs, miR-34a is important as it is often inactivated in cancer cells and acts as a tumor suppressor for various types of cancer. The reverse transcription-quantitative polymerase chain reaction (RT-qPCR) results confirmed that miR-34a was upregulated by HDAC1 knockdown. Cells depleted of HDAC1 had lower abilities to migrate, invade and adhere, which were restored by a miR-34a antagomiR. Depletion of HDAC1 also resulted in impaired microfilaments and microtubules, while co-transfection of the miR-34a antagomiR attenuated these changes in the cellular cytoskeleton. The HDAC1/miR-34a axis regulated the expression and activation of CD44 and its downstream factors including Bcl-2, Ras homolog family member A (RhoA), LIM domain kinase 1 (LIMK-1) and matrix metalloproteinase (MMP)-2. The latter three proteins were responsible for the organization of tubulin and actin cytoskeleton and the formation of cellular pseudopodia. In conclusion, results of the present study indicated that HDAC1 depletion inhibits the metastatic abilities of gastric cancer cells by regulating the miRNA-34a/CD44 pathway, which may be a potential target for the treatment of gastric cancer. IntroductionGastric cancer remains the fourth most common malignancy and the second leading cause of cancer-related mortality worldwide, although its incidence is gradually on the decrease in most parts of the world (1). The currently available chemotherapeutic agents have only limited benefits for most gastric cancer patients. Therefore, identification of novel targets and an understanding of their molecular mechanisms is crucial for the treatment of gastric cancer patients.Histone deacetylases (HDACs) are a class of enzymes that remove the acetyl groups from core histones, as well as non-histone proteins, such as p53 (2). By modifying the status of deacetylation, HDACs induce transcriptional repression through chromatin condensation and alteration of protein activity (3). Among the 18 HDAC family members, HDAC1 accounts for more than half of cellular HDAC activity, and cannot be compensated by other HDACs (4). HDAC1 acts at all levels of gene expression including microRNA (miRNA or miR) regulation (5). Overexpression of HDAC1 is significantly associated with higher lymphatic metastases and decreased 3-year survival rates in gastric cancer patients (6). Many HDAC inhibitors have been developed, several of which have shown promise and are under investigation in clinical trials (3,7). However, the underlying mechanisms for the anti-metastatic activities of HDAC inhibitors, particularly...

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“…MMP family members, which tumor cells secrete, can degrade all of the important extracellular matrix components. Studies have also shown that Skp2-RNAi downregulates MMP-2 (metalloproteinase-2) and MMP-9 (metalloproteinase-9) secretion and inhibits the invasion ability of tumors (25,26).…”

Section: Discussionmentioning

confidence: 99%

RNAi-Mediated Knockdown of Skp2 Inhibits Human Bladder Cancer Proliferation and Invasion in T24 Cells

Xiong

et al. 2016

Iran Red Crescent Med J

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Background: Skp2 (S-phase kinase-associated protein 2 is overexpressed in many kinds of cancers, and is related to the occurrence and development of tumors. The molecular mechanism of Skp2 in the regulation of bladder cancer cell biological behavior after Skp2 expression knockdown, however, has remained unknown. Objectives: In our present studies (experimental cytobiological studies, we used an RNAi approach to knock down Skp2 expression, and studied its impact on cell proliferation and invasion of T24 cells. Materials and Methods:The expression of the Skp2 gene was knocked down by RNA interference (RNAi) in T24 cells. The transcription level of Skp2 was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. The expression of Skp2, caspase-3, caspase-8, caspase-9, and p27 (p27 Kip1 ) were measured by western blot assay. Cell proliferation and apoptosis were

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Downregulation of Skp2 inhibits the growth and metastasis of gastric cancer cells in vitro and in vivo

Cited by 45 publications

References 40 publications

Interference of Skp2 effectively inhibits the development and metastasis of colon carcinoma

Interference of Skp2 effectively inhibits the development and metastasis of colon carcinoma

Depletion of histone deacetylase 1 inhibits metastatic abilities of gastric cancer cells by regulating the miR-34a/CD44 pathway

RNAi-Mediated Knockdown of Skp2 Inhibits Human Bladder Cancer Proliferation and Invasion in T24 Cells

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