A polymorphic minisatellite region of BORIS regulates gene expression and its rare variants correlate with lung cancer susceptibility

Yoon, Se-Lyun; Roh, Yun-Gil; Chu, In-Sun; Heo, Jeonghoon; Kim, Kyung Sik; Chang, Hee-Kyung; Kang, Tae-Hong; Chung, Jin Woong; Koh, Sang Seok; Larionov, Vladimir; Leem, Sun‐Hee

doi:10.1038/emm.2016.50

Cited by 10 publications

(5 citation statements)

References 33 publications

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“…also observed different behaviors of tumor cells upon aberrant expression of BORIS29. The isoform variants of BORIS may function differently in different cell backgrounds3031. Colorectal cancer is a heterogeneous multi-stage disease.…”

Section: Discussionmentioning

confidence: 99%

Brother of Regulator of Imprinted Sites (BORIS) suppresses apoptosis in colorectal cancer

Zhang

Fang

Song

et al. 2017

Sci Rep

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Identifying oncogenes that promote cancer cell proliferation or survival is critical for treatment of colorectal cancer. The Brother of Regulator of Imprinted Sites (BORIS) is frequently expressed in most types of cancer, but rarely in normal tissues. Aberrantly expressed BORIS relates to colorectal cancer, but its function in colorectal cancer cells remains unclear. In addition, previous studies indicated the significance of cytoplasm-localized BORIS in cancer cells. However, none of them investigated its function. Herein, we investigated the functions of BORIS in cancer cell proliferation and apoptosis and the role of cytoplasm-localized BORIS in colorectal cancer. BORIS expression correlated with colorectal cancer proliferation. BORIS overexpression promoted colorectal cancer cell growth, whereas BORIS knockdown suppressed cell proliferation. Sensitivity of colorectal cancer cells to 5-fluorouracil (5-FU) was inversely correlated with BORIS expression. These data suggest that BORIS functions as an oncogene in colorectal cancer. BORIS silencing induced reactive oxygen species (ROS) production and apoptosis, whereas BORIS supplementation inhibited apoptosis induced by BORIS short interfering RNA (siRNA), hydrogen peroxide (H2O2) or 5-FU. Introduction of BORIS-ZFdel showed that cytoplasmic localization of BORIS inhibited apoptosis but not ROS production. Our study highlights the anti-apoptotic function of BORIS in colorectal cancer.

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Section: Discussionmentioning

confidence: 99%

Brother of Regulator of Imprinted Sites (BORIS) suppresses apoptosis in colorectal cancer

Zhang

Fang

Song

et al. 2017

Sci Rep

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“…Since 5-FU or DDP induces DNA damage and apoptosis of carcinoma cells ( 9 – 11 ), BORIS may induce resistance to DDP therapy. Based on the prevalent expression of BORIS and the high incidence of DDP resistance in NSCLC ( 4 , 12 ), it is worth investigating whether BORIS contributes to DDP resistance in NSCLC.…”

Section: Introductionmentioning

confidence: 99%

Brother of regulator of imprinted sites inhibits cisplatin‑induced DNA damage in non‑small cell lung cancer

Zhang

Song

et al. 2020

Oncol Lett

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Cisplatin (DDP) chemotherapy is the primary modality of treatment for non-small cell lung cancer (NSCLC). However, due to the occurrence of DDP resistance, only a limited number of patients benefit from this treatment regimen. Brother of Regulator of Imprinted Sites (BORIS) is expressed elevated in NSCLC. Whether BORIS is involved in the DDP resistance of NSCLC is currently undetermined. The association between BORIS expression and overall survival rate of 156 patients with NSCLC who received DDP chemotherapy was analyzed in the present study. In order to investigate the function of BORIS in DDP chemotherapy, BORIS was silenced or overexpressed in four NSCLC cell lines. The cell viabilities, apoptosis and DNA damage induced by DDP were evaluated in these cell lines. In addition, the regulations of DNA repair genes were assessed, including POLH, ERCC1, BRCA1, MSH6 and XPA. The present study demonstrated that high BORIS expression was associated with decreased overall survival rate in patients with NSCLC who received DDP chemotherapy. The patients who benefited and went into remission following DDP therapy expressed a relatively low level of BORIS, suggesting the potential function of BORIS in DDP resistance. Cell experiments revealed that NSCLC cells that had a higher proliferation rate and resisted DDP treatment expressed a relatively higher level of BORIS. Knockdown of BORIS in NSCLC cells induced DNA damage; inhibiting cell proliferation and sensitizing cells to DDP treatment. In contrast, BORIS overexpression suppressed DDP-induced DNA damage. Notably, the mismatch repair factor mutS homolog 6 (MSH6) was regulated by BORIS, indicating its association with BORIS-associated DDP resistance in NSCLC. The findings of the present study suggest that BORIS suppresses DNA damage and promotes the progression of NSCLC and DDP resistance. The present study indicates the potential application of BORIS in NSCLC therapy and prognosis.

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“…Normally, it expresses only in testicular tissue participating in spermatogenesis. In multiple tumor tissues and cells, it also could be rehighly expressed, being involved in tumorigenesis, metastasis and invasion 2–4 . BORIS usually binds to the gene promoter region to regulate the expression of tumor related genes.…”

Section: Introductionmentioning

confidence: 99%

“…In multiple tumor tissues and cells, it also could be rehighly expressed, being involved in tumorigenesis, metastasis and invasion. [2][3][4] BORIS usually binds to the gene promoter region to regulate the expression of tumor related genes. Our previous study found that BORIS up-regulated the expression of Oct4 by increasing H3K4me2 and reducing H3K27me3, and promoted the stem cell-like properties in HCC cells.…”

Section: Introductionmentioning

confidence: 99%

BORIS variant SF2(C2/A4) promotes the malignant development of liver cancer by activating epithelial‐mesenchymal transition and hepatic stellate cells

Wei

Liu

Qin

et al. 2023

Molecular Carcinogenesis

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The underlying mechanisms of metastasis and recurrence of liver cancer remain largely unknown. Here, we found that Brother of the Regulator of Imprinted Sites (BORIS) variant SF2(C2/A4) was highly expressed in high metastatic potential hepatocellular carcinoma (HCC) cells and clinical tumor samples, related to the formation of satellite nodules. Its over expression promoted self-renewal, the expression of tumor stem cell markers, chemoresistance, wound healing rate, invasion and metastasis of HepG2 and Hep3B cells; reinforced epithelialmesenchymal transition (EMT), decreased the expression of E-cadherin and increased N-cadherin and Vimentin. Subcellular localization experiment showed that BORIS SF2(C2/A4) was localized in nucleus and cytoplasm. Further double luciferase reporter gene experiment confirmed that it bound to TWIST1 gene promoter and significantly increased latter expression. BORIS SF2(C2/A4) knock down induced apoptosis of HCCLM3 and PLC/PRF/5 cells, and increased the protein content of cleaved caspase 3. Additionally, BORIS SF2(C2/A4) over expression increased the expression of fibroblast growth factor 2 (FGF2) in HepG2 and Hep3B cells. FGF2 expressed higher in HCC tumor tissues than in paired peritumor tissues, and its expression was positively correlated with BORIS SF2(C2/A4).Interestingly, high expression of FGF2 is also associated with the formation of satellite nodules. Moreover, using the medium from BORIS SF2(C2/A4) overexpressed cell lines to coculture hepatic stellate cell (HSCs) line LX-2, the latter could be activated and increased the expression of CD90 and PIGF, which is consistent with the effect of adding bFGF alone. These results indicate that BORIS SF2(C2/A4) plays a role in deterioration of liver cancer by regulating TWIST1 to induce EMT, and by FGF2 to activate HSCs.

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A polymorphic minisatellite region of BORIS regulates gene expression and its rare variants correlate with lung cancer susceptibility

Cited by 10 publications

References 33 publications

Brother of Regulator of Imprinted Sites (BORIS) suppresses apoptosis in colorectal cancer

Brother of Regulator of Imprinted Sites (BORIS) suppresses apoptosis in colorectal cancer

Brother of regulator of imprinted sites inhibits cisplatin‑induced DNA damage in non‑small cell lung cancer

BORIS variant SF2(C2/A4) promotes the malignant development of liver cancer by activating epithelial‐mesenchymal transition and hepatic stellate cells

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