A <scp>TALEN</scp>‐based specific transcript knock‐down of <scp>PIWIL</scp>2 suppresses cell growth in HepG2 tumor cell

Chen, Y.; Hu, Weimin; Liu, Yanrong; Jiang, Shu; Li, C.; Chen, Jie; Tao, Dachang; Liu, Y.; Yang, Yanfei; Ma, Yongxin

doi:10.1111/cpr.12120

Cited by 17 publications

(10 citation statements)

References 39 publications

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“…Hepatocellular carcinoma (HCC) is believed to be one of the most common types of malignancy of the liver and has been reported as the fifth most prevalent cancer and third most frequent cause of cancer associated death worldwide [1, 2]. In spite of the therapeutic advances in diagnosis and clinical treatment, the 5-year survival rate of HCC across all cancer stages is still less than 30 % due to postoperative recurrence [3].…”

Section: Introductionmentioning

confidence: 99%

miR-34a Inhibits Cell Proliferation by Targeting SATB2 in Hepatocellular Carcinoma

Wang

et al. 2018

BioMed Research International

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Hepatocellular carcinoma (HCC) is the most common type of malignancy of the liver and has been reported as the third most frequent cause of cancer associated death worldwide. Accumulating evidence showed that the expression of miR-34a was abnormal in HCC patients; however, the role of miR-34a in HCC is not clear. In this study, we have observed low expression of the miR-34a in both HCC tissues and hepatoma cell line as compared to normal control. Further to investigate the role of miR-34a in HCC development, HepG2 cells were transfected with miR-34a mimic. Following transfection, miR-34a expression was significantly increased, which further repressed proliferation of HepG2 cells. Bioinformatics, Luciferase Reporter, RT-qPCR, and western blotting assays indicated that special AT-rich sequence-binding protein-2 (SATB2) is a direct target of miR-34a in HCC cells. There was a negative correlation between the expression levels of SATB2 and miR-34a. Investigation into the molecular mechanism indicated that miR-34a regulated cell proliferation through inhibiting SATB2. Therefore, the results of the present study may improve understanding regarding the role of miR-34a in regulating cell proliferation and contribute to the development of novel therapy of HCC.

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Section: Introductionmentioning

confidence: 99%

miR-34a Inhibits Cell Proliferation by Targeting SATB2 in Hepatocellular Carcinoma

Wang

et al. 2018

BioMed Research International

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“…Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer and the third most frequent cause of cancer mortality worldwide, leading to more than 600,000 deaths each year [ 1 , 2 ]. HCC is especially common in China, with the mortality rate the second highest [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

miR-211 suppresses hepatocellular carcinoma by downregulating SATB2

Jiang

Cui

et al. 2015

Oncotarget

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Dysregulation of microRNAs (miRs) is involved in carcinogenesis. Deregulation of miR-211 has recently been observed in many tumors, but its function in hepatocellular carcinoma (HCC) is still unknown. Here we found that miR-211 was decreased in HCC cancer tissues compared with adjacent normal tissues. We also found that overexpression of miR-211 repressed proliferation and invasion in HepG2 and SMMC7721 cells. Luciferase reporter assays and western blot indicated that special AT-rich sequence-binding protein-2 (SATB2), is a direct target of miR-211. The expression of SATB2 was upregulated in HCC cancer tissues and cell lines and miR-211 levels inversely correlated with SATB2 levels in HCC. Importantly, SATB2 rescued the miR-211-mediated inhibition of cell invasion and proliferation. Finally, reintroduction of miR-211 repressed tumor formation of HCC in xenograft mice. This study provides insights into molecular mechanisms that miR-211 contributed to HCC.

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“…In addition to gametogenesis [ 2 , 5 , 40 ], PIWIL2 can promote tumorigenesis through upregulating several signal transduction pathways [ 1 , 2 , 10 , 41 – 46 ] and inhibiting apoptotic death of tumor cells via activation of Stat3/Bcl-XL pathway [ 10 , 11 ]. However, these functions of PIWIL2 in tumor development remain controversial, because most of the commercial available antibodies specific for PIWIL2 could not distinguish the full length PIWIL2 from its variants [ 1 , 2 ].…”

Section: Discussionmentioning

confidence: 99%

An unusual intragenic promoter ofPIWIL2contributes to aberrant activation of oncogenicPL2L60

Liu

et al. 2017

Oncotarget

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PIWIL2-like (PL2L) protein 60 (PL2L60), a product of aberrantly activated PIWIL2 gene, is widely expressed in various types of tumors and may promote tumorigenesis. However, the mechanisms underlying the activation of expression of PL2L60 remain unknown. In this study, an intragenic promoter responsible for the activation of PL2L60 within the human PIWIL2 gene has been identified, cloned and characterized. The promoter of PL2L60 is located in the intron 10 of the host gene PIWIL2. Bioinformatic and mutagenic analysis reveals that this intragenic promoter within the sequence of 50 nucleotides contains two closely arranged cis-acting elements specific for the hepatic leukemia factor (HLF) in the positive strand and signal transducer and activator of transcription 3 (STAT3) in the negative strand. Chromatin immunoprecipitation analysis demonstrates that both the HLF and polymerase II (Pol II), a hallmark of active promoters, directly bind to the sequence, although STAT3 does not. Knockdown of HLF and STAT3 alone or both by RNA interference significantly reduced both promoter activity and the PL2L60 protein expression, although there is no additive effect. The expression of PL2L60 proteins was enhanced when host gene Piwil2 was genetically disrupted in a murine cell model. Taken together, we have identified a PL2L60-specific intragenic promoter in the host gene of PIWIL2, which is interdependently activated by HLF and STAT3 through steric interaction. This activation is dependent on cellular milieu rather than the integrity of host gene PIWIL2, highlighting a novel, important mechanism for a cancer-causing gene to be activated during tumorigenesis.

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A TALEN‐based specific transcript knock‐down of PIWIL2 suppresses cell growth in HepG2 tumor cell

Abstract: Taken together, our study revealed critical negative regulation of TGF-β signalling by PIWIL2 in HepG2 tumour cells, and provided an effective strategy to study specific gene transcript functions in cells.

Cited by 17 publications

References 39 publications

miR-34a Inhibits Cell Proliferation by Targeting SATB2 in Hepatocellular Carcinoma

miR-34a Inhibits Cell Proliferation by Targeting SATB2 in Hepatocellular Carcinoma

miR-211 suppresses hepatocellular carcinoma by downregulating SATB2

An unusual intragenic promoter ofPIWIL2contributes to aberrant activation of oncogenicPL2L60

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