Asparagine Synthetase and Filamin A Have Different Roles in Ovarian Cancer

Zeng, Liang; Wang, Qiong; Gu, Congmin; Li, Yuan; Xie, Xiaohui; Li, He; Chen, Kai; Tan, Pengfei; Xue, Lei; Huang, Sanqian; Shi, Kun

doi:10.3389/fonc.2019.01072

Cited by 10 publications

(8 citation statements)

References 40 publications

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“…OC is one of the three common malignant tumors of the female reproductive system that poses a serious threat to women's health. Because of the complex endocrine function of the ovary, the early OC symptoms are unspecific, so patients usually miss the optimum treatment window by the time they are diagnosed [10]. Recently, the OC incidence rate has increased significantly and patients tend to be younger at diagnosis.…”

Section: Discussionmentioning

confidence: 99%

Exosomal CA125 as A Promising Biomarker for Ovarian Cancer Diagnosis

Chen¹,

Liang²,

Zeng³

et al. 2020

J. Cancer

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The main diagnostic indicators of ovarian cancer (OC), including carbohydrate antigen 125 (CA125) and human epididymis protein 4 (HE4), show good sensitivity and poor specificity or vice versa. This study investigated changes in CA125 and HE4 expression and their correlation in serum-derived exosomes of 55 patients with OC (OC group), 33 patients with malignant tumors (non-OC group), and 55 normal controls (NC group). We compared serum and exosomal CA125 and HE4 levels to determine whether their contents in exosomes were elevated. We also compared the diagnostic efficacy of serum HE4, serum CA125, exosomal CA125, and serum HE4+exosomal CA125 in OC using the receiver operating characteristic (ROC) curve. CA125 levels in serum-derived exosomes in all groups significantly increased (P < 0.0001) compared with serum CA125 levels. HE4 was undetected in exosomes. The ROC curve showed the following values:

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Section: Discussionmentioning

confidence: 99%

Exosomal CA125 as A Promising Biomarker for Ovarian Cancer Diagnosis

Chen¹,

Liang²,

Zeng³

et al. 2020

J. Cancer

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“…The roles of FLNA in cisplatin remain largely unclear 44 , 45 . In the present study, we employed two distinct shRNAs targeting FLNA and a nontarget shRNA as a control to knock down FLNA in A549/DDP cells to further determine the biological function of FLNA in cisplatin chemoresistance.…”

Section: Resultsmentioning

confidence: 99%

TRIM44 promotes BRCA1 functions in HR repair to induce Cisplatin Chemoresistance in Lung Adenocarcinoma by Deubiquitinating FLNA

Zhang¹,

Cao²,

Shi³

et al. 2022

Int. J. Biol. Sci.

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Tripartite motif-containing 44 (TRIM44) has recently been implicated in various pathological processes in numerous cancers, including lung adenocarcinoma (LUAD); however, its functional roles in chemoresistance are poorly understood. Herein, TRIM44 knockdown sensitized LUAD cells to cisplatin and enhanced cisplatin-induced apoptosis. Microarray analysis indicated that the “ Role of BRCA1 in DNA damage ” and the BRCA1 gene expression were positively regulated by TRIM44, which was further verified by immunofluorescence, qRT-PCR, and Western blotting. BRCA1 depletion effectively abolished TRIM44-modulated cisplatin resistance and regulation of homologous recombination (HR) repair. Interestingly, TRIM44 interacted with FLNA, an upstream regulator of BRCA1 as specified by STRING V 11.5, and facilitated its stability and deubiquitination. FLNA was also found to be required for the functions of TRIM44 in drug resistance. Using animal models, overexpression of TRIM44 was shown to confer resistance to cisplatin in a BRCA1- and FLNA-dependent manner. TRIM44 expression levels in tissues from cisplatin-resistant LUAD patients were significantly higher than those in tissues from cisplatin-sensitive LUAD patients. Collectively, our study results demonstrate that the TRIM44/FLNA/BRCA1 axis is involved in cisplatin chemoresistance, providing potential therapeutic targets for LUAD patients with cisplatin resistance.

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“…Therefore, we speculate that FLNA plays an important role in tumor metastasis. Although FLNA was reported to be highly expressed in cancers ( 39 – 41 ), its connection with breast cancer metastasis has not been well investigated previously.…”

Section: Discussionmentioning

confidence: 99%

Filamin A Is a Potential Driver of Breast Cancer Metastasis via Regulation of MMP-1

Zhou

et al. 2022

Front. Oncol.

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Recurrent metastasis is a major fatal cause of breast cancer. Regretfully, the driving force and the molecular beneath have not been fully illustrated yet. In this study, a cohort of breast cancer patients with locoregional metastasis was recruited. For them, we collected the matched samples of the primary tumor and metastatic tumor, and then we determined the mutation profiles with whole-exome sequencing (WES). On basis of the profiles, we identified a list of deleterious variants in eight susceptible genes. Of them, filamin A (FLNA) was considered a potential driver gene of metastasis, and its low expression could enhance 5 years’ relapse survival rate by 15%. To prove the finding, we constructed a stable FLNA knockout tumor cell line, which manifested that the cell abilities of proliferation, migration, and invasion were significantly weakened in response to the gene knockout. Subsequently, xenograft mouse experiments further proved that FLNA knockout could inhibit local or distal metastasis. Putting all the results together, we consolidated that FLNA could be a potential driver gene to metastasis of breast cancer, in particular triple-negative breast cancer. Additional experiments also suggested that FLNA might intervene in metastasis via the regulation of MMP-1 expression. In summary, this study demonstrates that FLNA may play as a positive regulator in cancer proliferation and recurrence. It provides new insight into breast cancer metastasis and suggests a potential new therapeutic target for breast cancer therapy.

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Asparagine Synthetase and Filamin A Have Different Roles in Ovarian Cancer

Cited by 10 publications

References 40 publications

Exosomal CA125 as A Promising Biomarker for Ovarian Cancer Diagnosis

Exosomal CA125 as A Promising Biomarker for Ovarian Cancer Diagnosis

TRIM44 promotes BRCA1 functions in HR repair to induce Cisplatin Chemoresistance in Lung Adenocarcinoma by Deubiquitinating FLNA

Filamin A Is a Potential Driver of Breast Cancer Metastasis via Regulation of MMP-1

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