KLF9 suppresses gastric cancer cell invasion and metastasis through transcriptional inhibition of MMP28

Yang, Li; Sun, Qiang; Jiang, Mingchun; Li, Shuang; Zhang, Jiayu; Xu, Zhangqi; Guo, Dongyang; Gu, Tianning; Wang, Boya; Xiao, Lei; Zhou, Tian; Zhuo, Wei

doi:10.1096/fj.201802531r

Cited by 50 publications

(48 citation statements)

References 52 publications

(50 reference statements)

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“…Mechanistically, Li et al confirmed that KLF9 dramatically suppressed gastric cancer cell invasion and metastasis by repressing MMP28 transcription. 30 Kang et al asserted that KLF9 was reduced in CRC tumor tissues than matched normal mucosa tissues. 31 Not surprisingly, KLF9 was declined in CRC tissues when compared with paired no-tumor tissues.…”

Section: Discussionmentioning

confidence: 99%

<p>CircNOL10 Acts as a Sponge of miR-135a/b-5p in Suppressing Colorectal Cancer Progression via Regulating KLF9</p>

Zhang¹,

Zhang²,

Yi³

et al. 2020

OTT

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Background: Circular RNAs (circRNAs) have been documented as key regulators during progression of malignant human cancer, including colorectal cancer (CRC). However, the underlying molecular mechanisms of circNOL10 in CRC remain unclear. Methods: The real-time quantitative polymerase chain reaction was used to quantify the expression of circNOL10, miR-135a-5p, miR-135b-5p, and Krüppel-like factor 9 (KLF9). Kaplan-Meier curve was employed to assess the relationship between survival time of CRC patients and expression level of circNOL10. Cell ability of proliferation was measured by Cell Counting Kit8 and colony formation assays. Cell-cycle analysis was performed using flow cytometry assay. In addition, migration and invasion of CRC cell were examined with transwell analysis. The protein expression level was measured with Western blot assay. The interaction relationship of different molecules was analyzed by bioinformatics database and confirmed by dual-luciferase reporter, RNA immunoprecipitation, and RNA pulldown assay. The functional role of circNOL10 in vivo was determined by xenograft experiment. Results: CircNOL10 was decreased in CRC tissues and cells and was associated with poor outcomes. Gain-of-functional experiment revealed that overexpression of circNOL10 constrained proliferation, cell-cycle progression, migration, and invasion of CRC cells, which was abolished by overexpression of miR-135a-5p or miR-135b-5p. Additionally, miR-135a-5p and miR-135b-5p, targets of circNOL10, regulated KLF9 expression in a negative feedback. Consistently, the results of xenograft experiment suggested that overexpression of circNOL10 inhibited tumor growth in vivo. Conclusion: In summary, our results showed that circNOL10 impeded CRC development by mediating proliferation, cell cycle, migration, and invasion by sponging miR-135a-5p and miR-135b-5p, which provided new understanding for CRC treatment.

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Section: Discussionmentioning

confidence: 99%

<p>CircNOL10 Acts as a Sponge of miR-135a/b-5p in Suppressing Colorectal Cancer Progression via Regulating KLF9</p>

Zhang¹,

Zhang²,

Yi³

et al. 2020

OTT

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“…KLF proteins have important roles in the regulation of a wide variety of biological processes as well as human diseases, such as cancer [40]. KLF9 acts as a tumor suppressor which has been reported to suppress cell proliferation, migration, invasion [41][42][43]. Previous study also shows that KLF9 is downregulated and negatively associated with poor prognosis in human ccRCC [44].…”

Section: Discussionmentioning

confidence: 99%

Downregulation of SNX5 By KLF9 Leads to Clear Cell Renal Cell Carcinoma Progression By Inducing CD44 Internalization and Suppressing Epithelial-to-Mesenchymal Transition

Zhou

et al. 2021

Preprint

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Background: Aberrant expression of SNX5 can contribute to tumourigenesis, invasion, and metastasis of several human cancers. However, the clinicopathological and biological significance of SNX5 in clear cell renal cell carcinoma (ccRCC) remain unclear. The aim of this study was to examine the role of SNX5 in the progression of ccRCC.Methods: Immunohistochemical (IHC), Western blot, qRT-PCR, western blot, flow cytometry and immunofluorescence were used to detect the expression of indicated molecules. The biological role of SNX5 in ccRCC cells was evaluated by CCK8, colony formation, transwell assay, subcutaneous tumor formation as well as veil tail injection. ChIP assay and luciferase reporter assay were used to determine the direct binding of KLF9 to the promoter of the SNX5 gene.Results: SNX5 expression was downregulated in human ccRCC tissues. SNX5 expression was negatively correlated with tumor size, AJCC stage, tumor thrombus of inferior vena cava (IVC) and poor prognosis of ccRCC. Ectopic expression of SNX5 inhibited ccRCC cell proliferation and metastasis whereas knockdown of SNX5 increase these activities both in vitro and in vivo. Mechanistically, overexpression of SNX5 blocked internalization and intracellular trafficking of CD44 in ccRCC cells. Exogenous expression of CD44 partially rescued the inhibitory effects of SNX5 on the proliferation and invasion activity of ccRCC cells. Knockdown of SNX5 in ccRCC cells was associated with epithelial mesenchymal transition (EMT), including the down-regulation of E-cadherin, ZO-1 and Claudin-1 and the concomitant up-regulation of Snail and N-cadherin. In addition, SNX5 inhibited TGF-β-induced migration, invasion and EMT in ccRCC cells. Moreover, we observed a significant correlation between SNX5 expression and E-cadherin levels in ccRCC patients. In addition, KLF9 directly bound to the SNX5 promoter and increased SNX5 transcription. SNX5 expression was closely correlated with KLF9 expression in ccRCC. Moreover, we found that the combination of SNX5 and CD44 or E-cadherin or KLF9 was a more powerful predictor of poor prognosis than either parameter alone.Conclusion: Collectively, our data reveal a mechanism that KLF9-mediated SNX5 expression was associated with poor prognosis via trafficking of CD44 and promoting EMT in ccRCC. SNX5 may be a potential prognostic biomarker and therapeutic target for patients with ccRCC.

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“…For example, Li et al. demonstrated that KLF9 suppressed gastric cancer cell invasion and metastasis through inhibiting the level of MMP28 ( 38 ). In the present study, we found that KFL9 was down-regulated in SEM tissues, compared to paracarcinoma tissues.…”

Section: Discussionmentioning

confidence: 99%

miR-483-3p, Mediated by KLF9, Functions as Tumor Suppressor in Testicular Seminoma via Targeting MMP9

et al. 2021

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BackgroundSeminoma (SEM) is the most frequent testicular germ cell tumor with a high incidence in young men. The present study aims to explore the function and regulatory mechanism of miR-483-3p in SEM.MethodsRT-qPCR was performed to investigate miR-483-3p levels in SEM tissues. The effect of miR-483-3p on TCam-2 cells was assessed by CCK-8, colony formation, cell migration, and invasion assays. Luciferase reporter assays were performed to investigate the interaction between miR-483-3p and MMP9, and then the recovery experiments were performed. Moreover, the potential upstream regulator of miR-483-3p was predicted based on JASPAR database.ResultsmiR-483-3p was down-regulated in SEM tissues versus paracancerous normal tissues. The expression level of miR-483-3p was significantly associated with tumor stage by RT-qPCR. Functionally, miR-483-3p over-expression suppressed cell growth, migration, and invasion in SEM cell lines. Mechanically, miR-483-3p negatively regulated MMP9 by directly binding to its 3′-UTR. The over-expression of miR-483-3p could reverse the promoting role of MMP9 over-expression on the proliferation, migration, and invasion of TCam-2 cells. Moreover, KLF9 was identified as a potential upstream regulator of miR-483-3p and functions as a tumor suppressor.ConclusionsIn general, our study suggested that miR-483-3p could inhibit the cell growth, migration, and invasion of testicular SEM by targeting MMP9. Moreover, KLF9 is an upstream positive regulator of miR-483-3p and also functions as a tumor suppressor in SEM.

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KLF9 suppresses gastric cancer cell invasion and metastasis through transcriptional inhibition of MMP28

Cited by 50 publications

References 52 publications

<p>CircNOL10 Acts as a Sponge of miR-135a/b-5p in Suppressing Colorectal Cancer Progression via Regulating KLF9</p>

<p>CircNOL10 Acts as a Sponge of miR-135a/b-5p in Suppressing Colorectal Cancer Progression via Regulating KLF9</p>

Downregulation of SNX5 By KLF9 Leads to Clear Cell Renal Cell Carcinoma Progression By Inducing CD44 Internalization and Suppressing Epithelial-to-Mesenchymal Transition

miR-483-3p, Mediated by KLF9, Functions as Tumor Suppressor in Testicular Seminoma via Targeting MMP9

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