MicroRNA-10b regulates epithelial–mesenchymal transition by modulating KLF4/KLF11/Smads in hepatocellular carcinoma

Hujie, Gulibaha; Zhou, Sasha; Zhang, Hua; Qu, Jie; Xiong, Xiaowei; Hujie, Outikuer; Liao, Cheng-Gong; Yang, Shuai

doi:10.1186/s12935-018-0508-0

Cited by 34 publications

(22 citation statements)

References 27 publications

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“…Inhibition of miR1-10b arrested the cell cycle at S and G 2 /M phase, suggesting that miR-10b promoted cell cycle progression. Furthermore, miR-10b inhibited apoptosis and promoted tumor cell migration and invasion, which is consistent with the role of miR-10b in breast cancer and hepatocellular carcinoma (24,25).…”

Section: Discussionsupporting

confidence: 82%

Effect and mechanism of microRNA‑10b on proliferation and invasion of esophageal cancer cells

Liu

Salai

et al. 2019

Exp Ther Med

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MicroRNA (miR)-10b is highly expressed in esophageal cancer tissues and is associated with poor prognosis of esophageal cancer. However, the role and mechanism of miR-10b in esophageal cancer cells remains unclear, therefore, the present study aimed to investigate this. Esophageal cancer cells, TE-1 and EC9706, were transfected with miR-10b mimic, miR-10b inhibitor or incubated with transforming growth factor-β (TGF-β). MTT and EdU assays were used to detect cell proliferation. Flow cytometry was used to determine cell cycle analysis and apoptosis. Cell migration and invasion were also analyzed. Western blot analysis was used to detect protein levels and reverse transcription-quantitative PCR was used to analyze miR-10b expression. The present results demonstrated that, compared with the control group, miR-10b significantly promoted TE-1 and EC9706 cell proliferation. Compared with miR-10b inhibitor group and control group, miR-10b mimic promoted esophageal cancer cell cycle progression, inhibited apoptosis of esophageal cancer cells and promoted the migration and invasion of cells. The proliferation of esophageal cancer cells increased in a dose-dependent manner with TGF-β concentration. TGF-β treatment induced high expression of miR-10b in both cell lines. The miR-10b mimic + TGF-β group further promoted the migration and invasion of esophageal cancer cells. Western blot analysis determined that, compared with the control group, miR-10b mimic increased TGF-β expression. miR-10b mimic also inhibited the expression of phosphatase and tensin homolog (PTEN) in tumor cells. Compared with the control group, TGF-β inhibited the expression of PTEN with the miR-10b mimic + TGF-β group further inhibiting the PTEN. miR-10b inhibitor + TGF-β reversed the effect of TGF-β and miR-10b on PTEN. In conclusion, miR-10b promoted cell cycle progression, inhibited apoptosis and promoted the migration and invasion of esophageal cancer cells. The mechanism may be related to the upregulation of TGF-β and the downregulation of PTEN. The present findings suggested that miR-10b might be a potential therapeutic target for esophageal cancer.

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Section: Discussionsupporting

confidence: 82%

Effect and mechanism of microRNA‑10b on proliferation and invasion of esophageal cancer cells

Liu

Salai

et al. 2019

Exp Ther Med

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“…In previous studies, KLF11 supported TGF-β signaling by terminating the smad7 loop and activating smad3; thus exerting anti-proliferative and pro-apoptotic functions in epithelial ovarian, pancreatic and liver cancer cells [17][18][19][20]. In the process of TGF-βinduced EMT, KLF11 significantly promoted hepatocellular carcinoma local invasion and distant metastasis by binding to the Smad7 promoter and suppressing transcription of Smad7 or directly up-regulating Smad2/3 expression [21,23]. However, there are no reports on relationship between KLF11 and the EMT process in GC.…”

Section: Discussionmentioning

confidence: 89%

“…Previous studies have shown that KLF11 has significant influence on proliferation, differentiation and apoptosis in epithelial ovarian, pancreatic and liver cancer [17][18][19][20]. While KLF11 promotes local invasion and distant migration in the EMT process in hepatocellular carcinoma [21], its biological functions and relationship with EMT in gastric cancer are not clarified.…”

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confidence: 96%

KLF11 promotes gastric cancer invasion and migration by increasing Twist1 expression

Zhao

et al. 2019

neo

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Gastric cancer (GC) is a leading cause of global cancer-related death. The incidence and mortality rates of gastric cancer in China are second and third ranked in all forms of malignant tumors. Krüppel-like factor11 (KLF11) is a member of the KLF family, and previous studies have shown it significantly influences epithelial ovarian, pancreatic and liver cancer proliferation, differentiation and apoptosis. However, the expression and some biological functions of KLF11 in GC are still unclear. We therefore collected and analyzed the mRNA and protein expressions of KLF11 in 59 paired gastric cancer tissues and matched healthy gastric tissue samples. We then investigated the KLF 11 biological functions and potential mechanisms in BGC823 and HGC27 gastric cancer cell lines. Analysis of KLF11 in gastric cancer specimens confirmed up-regulation compared to adjacent healthy gastric tissues, and similar results were evident in the GC cell lines. Ectopic expression of KLF11 was significantly associated with GC cell invasion and migration. KLF11 functions were most effective in Twist1 expression and knockdown, and also in KLF11 up-regulation which was accompanied by corresponding change in Twist1 expression; but these effects were inhibited when KLF11 was silenced by the small interfering RNA (siRNA). The relative Twist1 promoter region activity increased gradually with increasing KLF11 plasma, and KLF11 therefore has a critical role in regulating gastric cancer migration and invasion by increasing Twist1 expression. Finally, the results of this study should improve understanding of the KLF11 and EMT regulating network and KLF11's use as a potential therapeutic target in gastric cancer.

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“…The internalization of exosomes enriched in miR-10b and miR-21 is able to increase proliferation in recipient HCC cells by increasing vimentin and Snail expression, while decreasing phosphatase and tensin homolog (PTEN) and E-cadherin [56]. In recipient cells, the increased vimentin expression and the synchronous E-cadherin repression are determined by miR-10b, targeting Kruppel Like Factor 4 (KLF4), which results in the activation of KLF11 and Small mother against pentaplegic proteins (Smads) to promote EMT [57]. At the same time, miR-21 suppresses PTEN, leading to the activation of AKT/ERK pathways and a consequent EMT [56].…”

Section: The Transfer Of Hcc-derived Exosomal Mirna Induces Neighbor mentioning

confidence: 99%

The Crosstalk between Tumor Cells and the Microenvironment in Hepatocellular Carcinoma: The Role of Exosomal microRNAs and Their Clinical Implications

Pascut

Pratama

Võ

et al. 2020

Cancers

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The communication between hepatocellular carcinoma (HCC) cells and their microenvironment is an essential mechanism supporting or preventing tumor development and progression. Recent evidence has identified extracellular vesicles (EVs) as one of the mechanisms mediating paracrine signaling between cells. Exosomes, the most described class of EVs, deliver proteins, mRNAs, noncoding RNAs, DNA, and lipids to recipient cells, also at remote distances. MicroRNAs (miRNAs), as part of the non-coding RNA exosomal cargo, have an important role in regulating cellular pathways in targeted cells, regulating several processes related to tumor progression invasion and metastasis, such as angiogenesis, immune-escape, epithelial-to-mesenchymal transition, invasion, and multi-drug resistance. Accumulating evidence suggests exosomal miRNAs as relevant players in the dynamic crosstalk among cancerous, immune, and stromal cells in establishing the tumorigenic microenvironment. In addition, they sustain the metastasic niche formation at distant sites. In this review, we summarized the recent findings on the role of the exosome-derived miRNAs in the cross-communication between tumor cells and different hepatic resident cells, with a focus on the molecular mechanisms responsible for the cell re-programming. In addition, we describe the clinical implication derived from the exosomal miRNA-driven immunomodulation to the current immunotherapy strategies and the molecular aspects influencing the resistance to therapeutic agents.

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MicroRNA-10b regulates epithelial–mesenchymal transition by modulating KLF4/KLF11/Smads in hepatocellular carcinoma

Cited by 34 publications

References 27 publications

Effect and mechanism of microRNA‑10b on proliferation and invasion of esophageal cancer cells

Effect and mechanism of microRNA‑10b on proliferation and invasion of esophageal cancer cells

KLF11 promotes gastric cancer invasion and migration by increasing Twist1 expression

The Crosstalk between Tumor Cells and the Microenvironment in Hepatocellular Carcinoma: The Role of Exosomal microRNAs and Their Clinical Implications

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