The transcriptional factor YY1 upregulates the novel invasion suppressor HLJ1 expression and inhibits cancer cell invasion

Wang, Chi Chung; Tsai, Meng Feng; Hong, Tse-Ming; Chang, Gee Chen; Chen, Chih Yi; Yang, Wen; Chen, Jeremy J.W.; Yang, Pan Chyr

doi:10.1038/sj.onc.1208573

Cited by 73 publications

(92 citation statements)

References 52 publications

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“…Because YY1 positively regulates expression of several oncogenes, that is, E6 and E7, c-Myc, c-Fos and ErbB2 (Riggs et al, 1993;Lee et al, 1995a, b), and negatively regulates p53 stability (Gronroos et al, 2004;Sui et al, 2004), it is believed that YY1 acts as an oncogene (Gordon et al, 2006;Castellano et al, 2009). On the other hand, YY1 also inhibits cancer cell growth through binding and inhibiting c-Myc function (Austen et al, 1998), and positively regulates expression of a number of genes with tumor suppressor function such as HLJ1, p73 and p53 (Furlong et al, 1996;Wang et al, 2005Wang et al, , 2007Wu et al, 2007a). These data suggest that YY1 can act as both a tumor suppressor and an oncogene, depending on tissue context and distribution of its downstream genes.…”

Section: Yy1 Activates Brca1 Transcription M-h Lee Et Almentioning

confidence: 99%

“…On the other hand, YY1 serves as a positive regulator for a number of genes with tumor suppressor function, such as DnaJ-like heat shock protein 40, HLJ1 (Wang et al, 2005(Wang et al, , 2007, p73 (Wu et al, 2007a) and p53 (Furlong et al, 1996) through various mechanisms. YY1 also acts as a negative regulator of cell growth through binding and inhibiting c-Myc function (Austen et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

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Yin Yang 1 positively regulates BRCA1 and inhibits mammary cancer formation

Lee

Lahusen

et al. 2011

Oncogene

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Expression of the breast cancer-associated gene 1 (BRCA1) in sporadic breast cancers is usually reduced, yet the underlying mechanisms remains elusive. To identify factors that are responsible for reduced BRCA1 expression, we screened 92 known transcription factors for their ability to regulate expression of BRCA1. Among several potential regulators, the Gli-Krueppel-related transcription factor Yin Yang 1 (YY1) showed the most dramatic transactivation of the BRCA1 promoter. YY1 binds to the promoter of BRCA1, and its overexpression resulted in increased expression of BRCA1 and a number of BRCA1 downstream genes. We further showed that overexpression of YY1 in cancer cells inhibited cell proliferation, foci formation and tumor growth in nude mice. To assess the clinical relevance between YY1 and BRCA1, we studied expression of YY1 and BRCA1 from human breast cancer samples and tissue arrays, and detected a significant positive correlation between the level of YY1 and BRCA1 expression in these cancers. Taken together, these findings suggest that YY1 is a key regulator of BRCA1 expression and may be causally linked to the molecular etiology of human breast cancer.

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Section: Yy1 Activates Brca1 Transcription M-h Lee Et Almentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Yin Yang 1 positively regulates BRCA1 and inhibits mammary cancer formation

Lee

Lahusen

et al. 2011

Oncogene

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“…Our in silico analysis (Li and Dahiya, 2002) showed that there are CpG islands in the 5¢-flanking region and in a region driving basal transcriptional activity of the HLJ1 gene (Wang et al, 2005). Those regions were designated as region-1 and region-2, respectively (Fig.…”

Section: Cpg Methylation In the 5¢-flanking Region Of Hlj1mentioning

confidence: 99%

“…There are several lines of evidence that collectively suggest HLJ1 as an antioncogenic factor: HLJ1 inhibits cell cycle progression through controlling the STAT1/P21 WAF1 pathway (Tsai et al, 2006), suppresses invasion by inducing E-Cadherin (Wang et al, 2005), and enhances apoptosis by activating JNK and CASPASE-3 . HLJ1 also suppresses malignancy by inhibiting the catalytic activity of SRC proto-oncogene (Chen et al, 2016).…”

mentioning

confidence: 99%

“…In this context, HLJ1 (DNAJB4) belongs to the DNAJ (HSP40) family of HSPs and is regarded as a tumor suppressor gene in lung, colon, and gastric cancers (Liu et al, 2014;Simões-correia et al, 2014;Tsai et al, 2006;Wang et al, 2005). HLJ1 has also been suggested as a potential biomarker and therapeutic target in lung cancer (Chen et al, 2008;Lai et al, 2013;Tsai et al, 2006;Wang et al, 2007).…”

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confidence: 99%

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HLJ1 (DNAJB4) Gene Is a Novel Biomarker Candidate in Breast Cancer

Acun

Doberstein

Habermann

et al. 2017

OMICS: A Journal of Integrative Biology

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Breast cancer is the most common cancer type and cause of cancer-related mortality among women worldwide. New biomarker discovery is crucial for diagnostic innovation and personalized medicine in breast cancer. Heat shock proteins (HSPs) have been increasingly reported as biomarkers and potential drug targets for cancers. HLJ1 (DNAJB4) belongs to the DNAJ (HSP40) family of HSPs and is regarded as a tumor suppressor gene in lung, colon, and gastric cancers. However, the role of the HLJ1 gene in breast cancer is currently unknown. We evaluated the role of the HLJ1 gene in breast cancer progression by analyzing its in vitro and in vivo expression and its genetic/epigenetic alterations. HLJ1 expression was found to be reduced or lost in breast cancer cell lines (SK-BR-3, MDA-MB-231, ZR-75-1) compared with the nontumorigenic mammary epithelial cell line (MCF 10A). In a clinical context for breast cancer progression, the HLJ1 expression was significantly less frequent in invasive breast carcinoma samples (n = 230) compared with normal breast tissue (n = 100), benign neoplasia (n = 53), and ductal carcinoma in situ (n = 21). In methylation analyses by the combined bisulfite restriction analysis assay, the CpG island located in the 5¢-flanking region of the HLJ1 gene was found to be methylated in breast cancer cell lines. HLJ1 expression was restored in the ZR-75-1 cell line by DNA demethylating agent 5-Aza-2¢-deoxycytidine (5-AzadC) and histone deacetylase inhibitor trichostatin A. These new observations support the idea that HLJ1 is a tumor suppressor candidate and potential biomarker for breast cancer. Epigenomic mechanisms such as CpG methylation and histone deacetylation might contribute to downregulation of HLJ1 expression. We call for future functional, epigenomic, and clinical studies to ascertain the contribution of HLJ1 to breast cancer pathogenesis and, importantly, evaluate its potential for biomarker development in support of personalized medicine diagnostic innovation in clinical oncology.

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Circulating TP73‐AS1 and CRNDE serve as diagnostic and prognostic biomarkers for non‐small cell lung cancer

et al. 2022

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Background: Circulating long noncoding RNAs (lncRNAs) are considered a new class of biomarkers for the diagnosis and prognosis of various malignancies.We aimed to identify circulating lncRNAs as biomarkers for the diagnosis and prognosis of non-small cell lung cancer (NSCLC). Methods: The expression of 14 candidate lncRNAs was measured in matched cancer and ipsilateral normal lung tissues of 20 patients with NSCLC using quantitative reverse-transcription PCR. In plasma samples from training and testing sets, significantly and aberrantly expressed lncRNAs, TA73-AS1 and CRNDE, were further analyzed. Receiver operating characteristic (ROC) curves were constructed, and the areas under the ROC curves (AUC) were obtained to assess diagnostic performance. The Kaplan-Meier survival analysis was used to assess the impact of plasma TA73-AS1 and CRNDE expression on tumor-free survival (TFS) of patients with NSCLC. The effect of TP73-AS1 expression on NSCLC cells was investigated in vitro. Results: AUC values of plasma TA73-AS1 and CRNDE were 0.822 and 0.815 in the training set and 0.843 and 0.804 in the testing set, respectively, to distinguish NSCLC from healthy controls. The combination of plasma TP73-AS1, CRNDE, and two classical tumor markers, carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1), showed excellent diagnostic performance for NSCLC (AUC =0.927 in the training set; AUC = 0.925 in the testing set). Furthermore, the high expression of the two plasma lncRNAs correlated with worse TFS in patients with NSCLC. In vitro cell model studies revealed that TP73-AS1 overexpression facilitated NSCLC cell survival, invasion, and migration. Conclusion: Circulating TP73-AS1 and CRNDE could be potential biomarkers for the diagnosis and prognostic prediction of NSCLC.

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The transcriptional factor YY1 upregulates the novel invasion suppressor HLJ1 expression and inhibits cancer cell invasion

Cited by 73 publications

References 52 publications

Yin Yang 1 positively regulates BRCA1 and inhibits mammary cancer formation

Yin Yang 1 positively regulates BRCA1 and inhibits mammary cancer formation

HLJ1 (DNAJB4) Gene Is a Novel Biomarker Candidate in Breast Cancer

Circulating TP73‐AS1 and CRNDE serve as diagnostic and prognostic biomarkers for non‐small cell lung cancer

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