Up-regulation of L Antigen Family Member 3 Associates With Aggressive Progression of Breast Cancer

Dong, Xubin; Lv, Shihui; Gu, Di; Zhang, Xiaohua; Ye, Zhiqiang

doi:10.3389/fonc.2020.553628

Cited by 3 publications

(12 citation statements)

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“…Since LAGE3 positively promotes the proliferation of HCC cells and breast cancer cells [ 9 , 11 ], our study involved CCK8 assay, BrdU assay, and cell cycle assay to explore the LAGE3 knockdown effects on the proliferation of HCC cells, and it was observed that the cell proliferation rate of the LAGE3-siRNA group was extraordinarily reduced in SMCC-7721 and Huh-7 cell lines when compared with the control group (Fig. 3 A, B).…”

Section: Resultsmentioning

confidence: 99%

“…Since LAGE3 positively promotes the migration and invasion of HCC cells and breast cancer cells [ 9 , 11 ], migration and invasion of cancer cells are the key driving force for cancer metastasis and the main cause of cancer-related deaths [ 15 , 16 ]. Therefore, scratch healing assay and Transwell assay were adopted to explore the effect of LAGE3 knockdown on the migration and invasion of HCC cells.…”

Section: Resultsmentioning

confidence: 99%

“…Many previous studies suggested that an abnormal LAGE3 expression was observed in an array of cells and organs undergoing malignant transformation [ 5 – 7 , 9 , 35 , 36 ]. In our study, TCGA database analysis revealed that when compared to normal liver tissues, an abnormally high level of LAGE3 expression was observed in LIHC tissues that indicated a poor survival prognosis for high LAGE3 expression patients; thus, pointing that LAGE3 may be a vital triggering factor in tumorigenesis and development of HCC.…”

Section: Discussionmentioning

confidence: 99%

“…A bioinformatics analysis study by Dong X et al revealed that since LAGE3 is highly expressed in breast cancer tissues, it can independently predict the survival of breast cancer patients. In contrast, the inhibition of LAGE3 expression can restrain the proliferation, migration, and invasion of triple-negative breast cancer cell lines and induce their apoptosis in vitro [ 9 ]. In our study, several lentiviral plasmids were applied to transfect HCC cells for silencing the LAGE3 gene, while qRT-PCR and western blot assays were procured to select the best knockdown efficiency and a good survival status cell line for the subsequent functional molecular target study.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have consistently observed that an extensive expression of LAGE3 is associated with poor prognosis and poor immune infiltration in patients with papillary thyroid carcinoma (PTC) and cutaneous melanoma (CM) [ 5 – 8 ]. Dong X et al found that LAGE3 enhanced the abilities of proliferation, migration, and invasion of cancer cells and resisted their apoptosis by activating intrinsic intracellular signaling pathways, thereby facilitating the development of breast cancer (BC) [ 9 ]. A study by Goswami T et al displayed that knockdown of LAGE3 affected cellular proliferation, thereby significantly reducing the growth of non-small cell lung cancer cells [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

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Correlation of LAGE3 with unfavorable prognosis and promoting tumor development in HCC via PI3K/AKT/mTOR and Ras/RAF/MAPK pathways

Xiong

2022

BMC Cancer

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Background Hepatocellular carcinoma (HCC) is one of the most common clinical malignancies quite susceptible to recurrence and metastasis. Despite several improvements in therapeutic approaches, the prognosis remains poor due to the limited treatment options. A bioinformatics analysis based on TCGA databases revealed that the recombinant human L antigen family member 3 (LAGE3) might function as an effective prognostic and diagnostic biomarker for HCC, as LAGE3, a protein-coding gene, maintains several important biological functions and has a physiological significance in the CTAG family while simultaneously being involved in regulating the occurrence and invasion of numerous types of tumors. However, the LAGE3 gene’s functional and regulatory mechanism in the progression of HCC remains unclear. Methods The LAGE3 level was investigated in 79 HCC tissues cases, ten HCC adjacent tissue cases, and six cases of normal liver tissues by IHC, while the LAGE3 level was evaluated in BEL-7404, SMCC-7721, Huh-7, HepG2, and MIHA cell lines by qRT-PCR and Western blot tests. Although the proliferation, migration, invasion, and apoptotic abilities of HCC cells were measured in vitro after silencing assay to probe the role of LAGE3 in HCC cells, the tumor xenograft growth experiment was used to verify the in vivo effect of LAGE3 gene knockdown on the growth of HCC tumors combined with bioinformatics analysis to study the LAGE3 mechanisms regulating HCC proliferation. Results Our results implied that LAGE3 was extensively expressed in HCC cell lines like BEL-7404, SMCC-7721, and Huh-7 cells as well as HCC tissues, but a lower expression was observed in HepG2 cells. Additionally, LAGE3 restrains cellular proliferation, promotes apoptotic pathways in HCC cells, and inhibits the growth of HCC tumors in vivo. Lastly, it was stated that LAGE3 might promote tumor development in HCC via PI3K/AKT/mTOR and Ras/RAF/MAPK pathways. Conclusion This study shows that the development of specific LAGE3 target drugs might become new effective treatment modalities for HCC patients.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Correlation of LAGE3 with unfavorable prognosis and promoting tumor development in HCC via PI3K/AKT/mTOR and Ras/RAF/MAPK pathways

Xiong

2022

BMC Cancer

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LAGE3 promoted cell proliferation, migration, and invasion and inhibited cell apoptosis of hepatocellular carcinoma by facilitating the JNK and ERK signaling pathway

Xing

Liu

et al. 2021

Cell Mol Biol Lett

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Background Hepatocellular carcinoma (HCC) is now the second leading cause of cancer death worldwide and lacks effectual therapy due to its high rate of tumor recurrence and metastasis. The aim of this study was to investigate the effects of L antigen family member 3 (LAGE3, a member of the LAGE gene family involved in positive transcription) on the progression of HCC. Methods The expression of LAGE3 was detected by quantitative real-time polymerase chain reaction. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony formation assay, EdU, and cell cycle analysis assay were employed to evaluate the proliferation of HCC cells. Annexin V-FITC/PI and TUNEL assay were used to assess the apoptosis rate of HCC cells. Wound healing and transwell assay were used to investigate the migration and invasion of HCC cells. A xenograft model of HCC was established with 2 × 106 Hep3B or SK-HEP1 cells to investigate the in vivo effects of LAGE3. Then, the protein levels of LAGE3, p-p38, p-38, c-Jun N-terminal kinase (JNK),p-JNK, extracellular signal-regulated kinase (ERK), and p-ERK were detected by western blot. Results We found that LAGE3 was upregulated in HCC tissues compared to adjacent tissues, and its high expression was correlated with poor overall survival by bioinformatics analysis. Next, we manually regulated the expression of LAGE3 in HCC cells. The knockdown of LAGE3 inhibited the proliferation of HCC cells by arresting the cell cycle in G1 phase. Also the downregulation of LAGE3 inhibited cell migration and invasion and induced apoptosis of HCC cells, while overexpression of LAGE3 promoted the malignant phenotypes of HCC. These results were further confirmed by the in vivo growth of HCC xenografts and the inhibition of apoptosis of HCC tumor cells. Furthermore, we found that LAGE3 exerted cancer-promoting effects by potentiating the JNK and ERK signaling pathway. An ERK inhibitor (10 μM SCH772984) or JNK inhibitor (25 μM SP600125) repressed the upregulated LAGE3-induced proliferation, migration, and invasion of HCC cells. Conclusions LAGE3 enhanced the malignant phenotypes of HCC by promoting the JNK and ERK signaling pathway.

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Analysis of L Antigen Family Member 3 as a Potential Biomarker and Therapeutic Target Associated With the Progression of Hepatocellular Carcinoma

Chen

Xie

et al. 2022

Front. Oncol.

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BackgroundHepatocellular carcinoma (HCC) is the third cause of cancer-related deaths worldwide. L antigen family member 3 (LAGE3) is a prognostic biomarker and associated with progression in a variety of tumors. However, little has been reported about the role and potential mechanism of LAGE3 in HCC.MethodsThe clinical value and function of LAGE3 in HCC were obtained from multiple online databases. The potential functions and pathways of LAGE3 in HCC were analysed by R package of “clusterProfiler”. LAGE3 knockdown cells were constructed in HepG2, HuH7 and MHCC97H cell lines, respectively. The biological roles of LAGE3 were examined by in vitro and in vivo experiments.ResultsLAGE3 was upregulated in HCC tissues compared with normal tissues, and high expression of LAGE3 was significantly associated with several clinical characteristics and indicated a worse prognosis of HCC. The co-expressed genes of LAGE3 could be enriched in the mTOR signaling pathway in HCC. LAGE3 was upregulated in HCC cell lines. Functionally, knocking down LAGE3 expression not only increased apoptosis and inhibited growth rate, cell death mediated by T cells, colony formation, migration and invasion ability of HCC cell lines in vitro, but also reduced the progression of HCC in the subcutaneous xenotransplanted tumor model.ConclusionOur results suggested that LAGE3 served as an oncogenic factor of HCC and could be a potential biomarker and therapeutic target for HCC.

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Up-regulation of L Antigen Family Member 3 Associates With Aggressive Progression of Breast Cancer

Cited by 3 publications

References 61 publications

Correlation of LAGE3 with unfavorable prognosis and promoting tumor development in HCC via PI3K/AKT/mTOR and Ras/RAF/MAPK pathways

Correlation of LAGE3 with unfavorable prognosis and promoting tumor development in HCC via PI3K/AKT/mTOR and Ras/RAF/MAPK pathways

LAGE3 promoted cell proliferation, migration, and invasion and inhibited cell apoptosis of hepatocellular carcinoma by facilitating the JNK and ERK signaling pathway

Analysis of L Antigen Family Member 3 as a Potential Biomarker and Therapeutic Target Associated With the Progression of Hepatocellular Carcinoma

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