MicroRNA-433 inhibits cell proliferation in hepatocellular carcinoma by targeting p21 activated kinase (PAK4)

Xue, Jing; Li, Zhan-Zhan; Hu, Ying-yun; Yan, Shipeng; Liu, Liya

doi:10.1007/s11010-014-2234-9

Cited by 30 publications

(25 citation statements)

References 29 publications

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“…Decreased miR-433 expression levels are correlated with distant metastasis and pathological TNM stage in patients with gastric cancer (21). MiR-433 downregulation has also been reported in colorectal cancer (22), hepatocellular carcinoma (23,24), myeloproliferative neoplasms (34), oral squamous cell carcinoma (35), ovarian cancer (36), retinoblastoma (37) and glioma (38). Conversely, miR-433 is overexpressed in osteosarcoma (39).…”

Section: Discussionmentioning

confidence: 95%

“…The findings of the present study suggested that miR-433 may be considered as a potential therapeutic target for the treatment of NSCLC. MiR-433 dysregulation is involved in numerous types of human cancer (21)(22)(23). For example, miR-433 is downregulated within gastric cancer tissues and cell lines (21).…”

Section: Discussionmentioning

confidence: 99%

“…MiR-433 is aberrantly expressed in numerous human cancers (21)(22)(23)(24); however, its expression pattern, biological functions and associated mechanisms in NSCLC require further investigation. The present study aimed to investigate the expression of miR-433 and determine its roles and underlying mechanisms in NSCLC.…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA‑433 reduces cell proliferation and invasion in non‑small cell lung cancer via directly targeting E2F transcription factor 3

Liu

Zhang

et al. 2018

Mol Med Report

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MicroRNAs (miRNA/miRs) have been associated with the initiation and progression of non‑small‑cell lung cancer (NSCLC). Hence, a comprehensive understanding of the association between dysregulated miRNAs and NSCLC may contribute to the identification of novel therapeutic methods for patients with NSCLC. MiRNA‑433 (miR‑433) has been reported to be dysregulated in numerous types of human cancers; however, its expression pattern, biological roles and associated mechanisms in NSCLC require further investigation. The present study aimed to detect miR‑433 expression and determine its roles and underlying molecular mechanisms in NSCLC. In the present study, reverse transcription‑quantitative polymerase chain reaction revealed that miR‑433 was significantly downregulated in NSCLC tissues and cell lines. This decreased miR‑433 expression was strongly associated with the tumor node metastasis stage and lymph node metastasis of patients with NSCLC. Cell Counting kit‑8 and cell invasion assays revealed that the resumption of miR‑433 expression decreased the proliferation and invasion of NSCLC cells. Bioinformatics analysis predicted E2F transcription factor 3 (E2F3) as a potential target of miR‑433. Luciferase reporter assay, RT‑qPCR and western blot analysis further demonstrated that E2F3 was a direct target of miR‑433 in NSCLC. E2F3 downregulation induced by small interfering RNA exhibited inhibitory effects similar to those of miR‑433 overexpression in NSCLC cells, and the restored E2F3 expression counteracted the suppressive effects on NSCLC cells induced by miR‑433 overexpression. Therefore, miR‑433 may inhibit the progression of NSCLC, at least in part, by targeting E2F3. The present study indicated that miR‑433 may be investigated as an innovative candidate target for the therapy of patients with this fatal disease.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

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MicroRNA‑433 reduces cell proliferation and invasion in non‑small cell lung cancer via directly targeting E2F transcription factor 3

Liu

Zhang

et al. 2018

Mol Med Report

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“…PAK4 modulation of CRAF and BAD phosphorylation inhibits apoptosis in endothelial cells (Alavi et al, 2003). The biology of PAK4 overexpressing cancer cells has also been shown to be regulated by PAK4 targeting by miR-199a/b-3p (Hou et al, 2011), miR-433 (Xue et al, 2015), and miR-224 (Li et al, 2014) in hepatocellular carcinoma cells. PAK4 also phosphorylates Smad2 on Ser465 in growth factor-stimulated cancer cells (Wang et al, 2014).…”

Section: Pak1 and Pak4 In Cancer Progressionmentioning

confidence: 99%

Structure, biochemistry, and biology of PAK kinases

Kumar

Sanawar

et al. 2017

Gene

174

192

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PAKs, p21-activated kinases, play central roles and act as converging junctions for discrete signals elicited on the cell surface and for a number of intracellular signaling cascades. PAKs phosphorylate a vast number of substrates and act by remodeling cytoskeleton, employing scaffolding, and relocating to distinct subcellular compartments. PAKs affect wide range of processes that are crucial to the cell from regulation of cell motility, survival, redox, metabolism, cell cycle, proliferation, transformation, stress, inflammation, to gene expression. Understandably, their dysregulation disrupts cellular homeostasis and severely impacts key cell functions, and many of those are implicated in a number of human diseases including cancers, neurological disorders, and cardiac disorders. Here we provide an overview of the members of the PAK family and their current status. We give special emphasis to PAK1 and PAK4, the prototypes of groups I and II, for their profound roles in cancer, the nervous system, and the heart. We also highlight other family members. We provide our perspective on the current advancements, their growing importance as strategic therapeutic targets, and our vision on the future of PAKs.

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“…Recent studies have shown that miR-433-3p, a tumor suppressor located on chromosome 12, inhibited the proliferation, invasion, and drug resistance of various tumor cells, and repressed the growth of hepatocellular carcinoma cells [5, 6]. Yang et al that miR-433-3p blocked the invasion of liver cancer cells [7].…”

Section: Introductionmentioning

confidence: 99%

MiR-433-3p Inhibits Proliferation and Invasion of Esophageal Squamous Cell Carcinoma by Targeting GRB2

Shi

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: MicroRNAs (miRNAs) are non-coding single stranded RNAs of 17-25 nucleotides in size, and their altered expression has been observed in various cancers. Previous studies have confirmed that miR-433-3p has effects on cancer cell proliferation, invasion, and migration, and its expression also correlates with sensitivity to chemotherapy. However, to date, there have been no studies on the biological functions of miR-433-3p in esophageal squamous cell carcinoma (ESCC). Methods: The Cell Counting Kit-8, transwell, and matrigel assays were used to test the effects of miR-433-3p and its predicted target, growth factor receptor-bound protein 2 (GRB2), on the proliferation, migration, and invasion of Eca109 and KYSE30 cells, two types of esophageal cancer cell lines. The miR-433-3p binding site in the 3′ untranslated region (UTR) region of GRB2 was predicted and verified using miRNA target site prediction software and structuring correct mutant examination. Western blotting and fluorescent quantitative PCR (FQ-PCR) techniques were employed to evaluate GRB2 expression. The inhibitory effects of miR-433-3p on tumor growth were investigated using a tumor xenograft model. Results: The binding site of miR-433-3p was identified in the 3′UTR region of GRB2. Western blotting and FQ-PCR showed that miR-433-3p inhibited the mRNA and protein expression of GRB2. Overexpression of GRB2 inhibited tumorigenesis in nude mice. MiR-433-3p overexpression inhibited the proliferation, migration, and invasion of ESCC cells by suppressing GRB2 gene expression. Conclusions: Our findings suggest that targeting miR-433-3p may have therapeutic benefits in ESCC.

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MicroRNA-433 inhibits cell proliferation in hepatocellular carcinoma by targeting p21 activated kinase (PAK4)

Cited by 30 publications

References 29 publications

MicroRNA‑433 reduces cell proliferation and invasion in non‑small cell lung cancer via directly targeting E2F transcription factor 3

MicroRNA‑433 reduces cell proliferation and invasion in non‑small cell lung cancer via directly targeting E2F transcription factor 3

Structure, biochemistry, and biology of PAK kinases

MiR-433-3p Inhibits Proliferation and Invasion of Esophageal Squamous Cell Carcinoma by Targeting GRB2

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