Lentivirus-delivered Krüppel-like factor 8 small interfering RNA inhibits gastric cancer cell growth in vitro and in vivo

Liu, Huan; Liu, Na; Xu, Min; Liu, Yi; Min, Jie; Pang, Hailin; Zhang, Ning; Zhang, Hongbo; Zhang, Helong

doi:10.1007/s13277-011-0245-7

Cited by 26 publications

(26 citation statements)

References 21 publications

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“…Various KLF8 transcripts have been identified, and the relative levels of the transcript expression appear to be similar to that in various tissues. In a previous study, we confirmed that KLF8 is important in SGC7901 gastric cell progression in vitro and in vivo (12). However, its underlying role in SGC7901 cells with invasion and migration under normoxic or hypoxic conditions have yet to be adequately elucidated.…”

Section: Discussionsupporting

confidence: 68%

“…A non-targeting stem-loop DNA PsicoR vector was generated as a negative control. Lentiviral particles were prepared as previously described (12). Gastric cancer cells were infected with KLF8 cDNA, siRNA-lentivirus or negative control virus at 7 days and examined at 10 days.…”

Section: Klf8 Cdna Vector and Rnai Lentivirus Generationmentioning

confidence: 99%

“…The continuous proliferation of tumor cells results in the center portion of hypoxia, which greatly promotes EMT (10,11). The results of a previous study demonstrated that KLF8 was highly expressed in gastric cancer tissues and exhibited a poor prognosis (12). KLF8 was initially identified as a transcription repressor of Krüppel-like C2H2 zinc-finger transcription factor family proteins (13).…”

Section: Introductionmentioning

confidence: 99%

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Krüppel-like factor 8 involved in hypoxia promotes the invasion and metastasis of gastric cancer via epithelial to mesenchymal transition

Liu¹,

Wang²,

Zhou³

et al. 2014

Oncology Reports

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Abstract. Previously, we reported that hypoxia was able to induce invasion and metastasis in gastric cancer and that hypoxia-inducible factor-1 (HIF-1) is a key factor involved in this tumor type. Krüppel-like factor 8 (KLF8) as a transcriptional repressor has been suggested as a promoter of tumor metastasis in breast cancer and an inducer of the epithelial-mesenchymal transition (EMT). KLF8 is also highly expressed in gastric cancer tissues, contributing to poor prognosis. However, the association between KLF8 and HIF-1 in regulating the progression of human gastric cancer in hypoxia is unclear. In the present study, we found that KLF8 was overexpressed in gastric cancer metastatic tissues and cells. Additionally, KLF8 siRNA significantly inhibited SGC7901 cell invasion and migration compared with SGC7901, SGC7901/Scr-si cells. Hypoxia is thus able to induce KLF8 expression and EMT in SGC7901 cells. However, following the examination of changes in cell morphology and epithelial and mesenchymal markers, it was found that KLF8 siRNA and HIF-1 siRNA strongly reversed EMT in cells undergoing hypoxia. Furthermore, hypoxia-induced KLF8 overexpression was attenuated by HIF-1 siRNA. Experiments using luciferase promoter constructs resulted in a marked increase in the activity of cells exposed to hypoxia and decreased activity in cells co-transfected with HIF-1 siRNA. The chromatin immunoprecipitation assay revealed proximal HRE at -133 is the main HIF-1 binding site in the KLF8 promoter.In conclusion, the results demonstrated that KLF8 is actively enhanced by hypoxia and is a novel HIF-1 target. KLF8 is a novel EMT regulating transcription factor that involved in the progression of gastric cancer. The specific anti-EMT drugs in combination with anti-hypoxia are new promising cancer therapies.

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Section: Discussionsupporting

confidence: 68%

Section: Klf8 Cdna Vector and Rnai Lentivirus Generationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Krüppel-like factor 8 involved in hypoxia promotes the invasion and metastasis of gastric cancer via epithelial to mesenchymal transition

Liu¹,

Wang²,

Zhou³

et al. 2014

Oncology Reports

Self Cite

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“…As a GT-box (CACCC) binding dual-transcription factor, KLF8 regulates the transcription of numerous genes by recruiting the C-terminal binding protein (CtBP) corepressor (6-10) or p300 and P300/CtBP-associated factor histone acetyltransferase co-activators (8,(11)(12)(13)(14) in order to target gene promoters. It is aberrantly overexpressed in a number of cancer subtypes and has been implicated in the initiation, development and progression of these cancer subtypes, including hepatocellular carcinoma (15)(16)(17), gastric cancer (18)(19)(20)(21), breast cancer (22,23), ovarian cancer (14,24), renal cancer (22,25) and glioma (26). It is worth noting that KLF8 induced tumor cell epithelial-to-mesenchymal transition (EMT) and maintained the invasive potential of cancer, which appeared to serve a critical role in the metastatic progression of cancer cells (6,27).…”

Section: Introductionmentioning

confidence: 99%

Krüppel-like factor 8 induces epithelial-to-mesenchymal transition and promotes invasion of pancreatic cancer cells through transcriptional activation of four and a half LIM-only protein 2

Zai

Long

et al. 2017

Oncology Letters

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Abstract. Pancreatic cancer (PC) is one of the most aggressive types of cancer with an extremely poor prognosis. Invasive growth and early metastasis is one of the greatest challenges to overcome for the treatment of PC. Numerous previous studies have indicated that the transcription factor Krüppel-like factor 8 (KLF8) and nuclear cofactor four and a half LIM-only protein 2 (FHL2) serve important roles in tumorigenesis and tumor progression; however, their roles in PC remain elusive. The present study revealed that KLF8 and FHL2 expression is aberrantly co-overexpressed in PC tissue samples and associa ted with tumor metastasis. Furthermore, a positive correlation between the expression levels of KLF8 and FHL2 was observed. Subsequently, the present study identified KLF8 as a critical inducer of epithelial-to-mesenchymal transition (EMT) and invasion. Of note, the present study demonstrated that KLF8 overexpression induced a strong increase in FHL2 expression, and subsequent promoter reporter assays determined that KLF8 directly bound and activated the FHL2 gene promoter. Furthermore, FHL2 knockdown in KLF8-overexpressing cells partially reversed the EMT and invasive phenotypes. The present study identified KLF8-induced FHL2 activation as a novel and critical signaling mechanism underlying human PC invasion.

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“…In addition, KLF8 has been shown to activate transcription from some gene promoters (21)(22)(23)(24). KLF8 is not expressed at readily detectable levels in most cell and tissue types studied to date (55), but numerous studies have reported its upregulation in various human cancers, including prostate (56), gastric (57,58), hepatocellular (59,60), glioma (61), breast (62,63), renal (64), and ovarian (65). KLF8 has been shown to regulate oncogenesis by promoting cellular proliferation and tumor invasion and by inhibiting apoptosis (21,(65)(66)(67)(68) Crossing these mice with Klf3 null mice results in embryonic lethality, indicative of a genetic interaction between these two factors.…”

mentioning

confidence: 99%

Generation of Mice Deficient in both KLF3/BKLF and KLF8 Reveals a Genetic Interaction and a Role for These Factors in Embryonic Globin Gene Silencing

Funnell

Mak

Twine

et al. 2013

Molecular and Cellular Biology

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f Krüppel-like factors 3 and 8 (KLF3 and KLF8) are highly related transcriptional regulators that bind to similar sequences of DNA. We have previously shown that in erythroid cells there is a regulatory hierarchy within the KLF family, whereby KLF1 drives the expression of both the Klf3 and Klf8 genes and KLF3 in turn represses Klf8 expression. While the erythroid roles of KLF1 and KLF3 have been explored, the contribution of KLF8 to this regulatory network has been unknown. To investigate this, we have generated a mouse model with disrupted KLF8 expression. While these mice are viable, albeit with a reduced life span, mice lacking both KLF3 and KLF8 die at around embryonic day 14.5 (E14.5), indicative of a genetic interaction between these two factors. In the fetal liver, Klf3 Klf8 double mutant embryos exhibit greater dysregulation of gene expression than either of the two single mutants. In particular, we observe derepression of embryonic, but not adult, globin expression. Taken together, these results suggest that KLF3 and KLF8 have overlapping roles in vivo and participate in the silencing of embryonic globin expression during development.

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Lentivirus-delivered Krüppel-like factor 8 small interfering RNA inhibits gastric cancer cell growth in vitro and in vivo

Cited by 26 publications

References 21 publications

Krüppel-like factor 8 involved in hypoxia promotes the invasion and metastasis of gastric cancer via epithelial to mesenchymal transition

Krüppel-like factor 8 involved in hypoxia promotes the invasion and metastasis of gastric cancer via epithelial to mesenchymal transition

Krüppel-like factor 8 induces epithelial-to-mesenchymal transition and promotes invasion of pancreatic cancer cells through transcriptional activation of four and a half LIM-only protein 2

Generation of Mice Deficient in both KLF3/BKLF and KLF8 Reveals a Genetic Interaction and a Role for These Factors in Embryonic Globin Gene Silencing

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