Ovarian seromucinous carcinoma: an independent epithelial ovarian cancer?

BACKGROUND: 2020 World Health Organization Classification of Female Genital Tumors removed ovarian seromucinous carcinoma as a distinct entity and recategorized it as ovarian endometrioid carcinoma with mucinous differentiation according to its pathological features. The aim of this study was to find whether ovarian seromucinous carcinoma truly represented a distinct category of ovarian tumors or an analogue of ovarian endometrioid carcinoma. METHODS: Twelve patients diagnosed with ovarian seromucinous carcinoma and received surgery at the Xiangya Hospital from January 2010 to December 2019 were included in this study. Clinicopathological features such as clinical symptoms, serological indicators, surgical information, postoperative findings, chemotherapy sensitivity, follow-up information, HE staining and IHC staining images and other clinicopathologic features were collected. Using t-test and Kaplan Meier to perform statistical analysis. Pathological review was conducted using the 2014 World Health Organization criteria. All pathological diagnoses were reviewed by two experienced pathologists. RESULTS: The age of 12 patients diagnosed with ovarian seromucinous carcinoma ranged from 23 to 68 years, with a median age of 46.8 years. Serum level of CA125 was elevated in 10 patients, and CA125/CEA ratio was less than 25 in 6 patients. Eleven patients underwent radical ovarian cancer surgery, and one patient underwent fertility preservation surgery. The progression free survival and overall survival of ovarian seromucinous carcinoma is 46.8 months and 50.2 months. Kaplan-Meier survival curve showed that the prognosis of ovarian seromucinous carcinoma and ovarian endometrioid carcinoma was significantly different (P = 0.03). The prognosis of ovarian seromucinous carcinoma and ovarian mucinous carcinoma was similar. CONCLUSION: Although ovarian seromucinous carcinoma and ovarian endometrioid carcinoma are similar in pathologic morphology, their clinical features and prognosis are significantly different. The signs, serum biomarker and prognosis of the ovarian seromucinous carcinoma are similar with ovarian mucinous carcinoma. Therefore, ovarian seromucinous carcinoma is not suitable to be directly classified as ovarian endometrioid carcinoma.

Development and validation of MRI-based model for the preoperative prediction of macrotrabecular hepatocellular carcinoma subtype.

BACKGROUND: Macrotrabecular hepatocellular carcinoma (MTHCC) has a poor prognosis and is difficult to diagnose preoperatively. The purpose is to build and validate MRI-based models to predict the MTHCC subtype. METHODS: Two hundred eight patients with confirmed HCC were enrolled. Three models (model 1: clinicoradiologic model; model 2: fusion radiomics signature; model 3: combined model 1 and model 2) were built based on their clinical data and MR images to predict MTHCC in training and validation cohorts. The performance of the models was assessed using the area under the curve (AUC). The clinical utility of the models was estimated by decision curve analysis (DCA). A nomogram was constructed, and its calibration was evaluated. RESULTS: Model 1 is easier to build than models 2 and 3, with a good AUC of 0.773 (95% CI 0.696-0.838) and 0.801 (95% CI 0.681-0.891) in predicting MTHCC in training and validation cohorts, respectively. It performed slightly superior to model 2 in both training (AUC 0.747; 95% CI 0.689-0.806; p = 0.548) and validation (AUC 0.718; 95% CI 0.618-0.810; p = 0.089) cohorts and was similar to model 3 in the validation (AUC 0.866; 95% CI 0.801-0.928; p = 0.321) but inferior in the training (AUC 0.889; 95% CI 0.851-0.926; p = 0.001) cohorts. The DCA of model 1 had a higher net benefit than the treat-all and treat-none strategy at a threshold probability of 10%. The calibration curves of model 1 closely aligned with the true MTHCC rates in the training (p = 0.355) and validation sets (p = 0.364). CONCLUSION: The clinicoradiologic model has a good performance in diagnosing MTHCC, and it is simpler and easier to implement, making it a valuable tool for pretherapeutic decision-making in patients.

DNA Repair Protein HELQ and XAB2 as Chemoresponse and Prognosis Biomarkers in Ascites Tumor Cells of High-Grade Serous Ovarian Cancer.

Nucleotide excision repair (NER) is an important mediator for responsiveness of platinum-based chemotherapy. Our study is aimed at investigating the NER-related genes expression in ascites tumor cells and its application in the prediction of chemoresponse in high-grade serous ovarian cancer (HGSC) patients. The relationship between 16 NER-related genes and the prognosis of ovarian cancer was analyzed in the TCGA database. NER-related genes including HELQ and XAB2 expressions were determined via immunocytochemistry in ascites cell samples from 92 ovarian cancer patients prior to primary cytoreduction surgery. Kaplan-Meier analysis and Cox model were used to investigate the association between NER-related gene expression and prognosis/chemotherapeutic response. Predicting models were constructed using a training cohort of 60 patients and validated in a validation cohort of 32 patients. We found that high expression of HELQ and XAB2 in the training cohort was associated with poor prognosis (for HELQ, P = 0.001, HR = 2.83, 95% CI: 1.46-5.49; for XAB2, P = 0.008, HR = 2.38, 95% CI: 1.23-4.63) and platinum resistance (for HELQ, P < 0.001; for XAB2, P = 0.006). In the validation cohort, the combination of HELQ and XAB2 (AUC = 0.863) showed the highest AUC. The expression levels of HELQ (RR 5.7, 95% CI 1.7-19.2) and XAB2 (RR 3.2, 95% CI 0.9-10.8) in ascites tumor cells were positively correlated to the risk of platinum resistance. In summary, we revealed that the expression levels of HELQ and XAB2 are candidate predictors for primary chemotherapy responsiveness and prognosis in HGSC. Ascites cytology is applicable as a promising method for chemosensitivity prediction in HGSC.

FOSL1 promotes proneural-to-mesenchymal transition of glioblastoma stem cells via UBC9/CYLD/NF-κB axis.

Proneural (PN) to mesenchymal (MES) transition (PMT) is a crucial phenotypic shift in glioblastoma stem cells (GSCs). However, the mechanisms driving this process remain poorly understood. Here, we report that Fos-like antigen 1 (FOSL1), a component of AP1 transcription factor complexes, is a key player in regulating PMT. FOSL1 is predominantly expressed in the MES subtype, but not PN subtype, of GSCs. Knocking down FOSL1 expression in MES GSCs leads to the loss of MES features and tumor-initiating ability, whereas ectopic expression of FOSL1 in PN GSCs is able to induce PMT and maintain MES features. Moreover, FOSL1 facilitates ionizing radiation (IR)-induced PMT and radioresistance of PN GSCs. Inhibition of FOSL1 enhances the anti-tumor effects of IR by preventing IR-induced PMT. Mechanistically, we find that FOSL1 promotes UBC9-dependent CYLD SUMOylation, thereby inducing K63-linked polyubiquitination of major nuclear factor κB (NF-κB) intermediaries and subsequent NF-κB activation, which results in PMT induction in GSCs. Our study underscores the importance of FOSL1 in the regulation of PMT and suggests that therapeutic targeting of FOSL1 holds promise to attenuate molecular subtype switching in patients with glioblastomas.

Molecular alterations and clinical relevance in cervical carcinoma and precursors (Review).

Cervical cancer is one of the most common types of cancer and the fourth leading cause of cancer­related deaths in women. The occurrence and development of cervical cancer is a multifactorial and multilevel process, which usually occurs alongside a continuous high­risk human papillomavirus infection. With further developments in molecular biology and the advancement of sequencing technology, the role of biomarkers in cervical diseases has been gradually recognized. Therefore, it remains a priority to identify key molecular markers that can be used for the screening and triaging of the lesions. In recent years, numerous studies have been conducted in order to identify important markers for cervical diseases. The present review aimed to summarize the molecular alterations and clinical relevance of chromosomal alterations, DNA polymorphisms, the DNA methylation status, histone modifications, and alterations in microRNA and protein expression levels. Accumulating evidence suggests that molecular alterations may reflect the degree and the prognosis of the disease. Although significant progress has been made in the field of cervical cancer research, further samples and experiments are still required to identify crucial molecules.

Correction to: Mass spectrometry-based proteomic capture of proteins bound to the MACC1 promoter in colon cancer.

In the original publication of the article, Acknowledgements section was published incorrectly. The correct Acknowledgements is given in this Correction.

Mass spectrometry-based proteomic capture of proteins bound to the MACC1 promoter in colon cancer.

MACC1 (metastasis associated in colon cancer 1) is a key driver that induces metastasis in colon cancer. However, the mechanisms by which MACC1 expression is transcriptionally regulated and the factors enriched at the MACC1 promoter remain largely unknown. The binding of proteins to specific DNA sites in the genome is a major determinant of genomic maintenance and the regulation of specific genes. The study herein utilized two methods to study the binding proteins of the MACC1 promoter region in colon cancer. Specifically, we adopted CRISPR-based chromatin affinity purification with mass spectrometry (CRISPR-ChAP-MS) and a biotin-streptavidin pulldown assay coupled with MS to identify the specific proteome bound to the MACC1 promoter in two colon cell lines with different metastatic potential. A total of 24 proteins were identified by CRISPR-ChAP-MS as binding to the MACC1 promoter, among which c-JUN was validated by ChIP-PCR. A total of 739 binding protein candidates were identified by biotin-streptavidin pulldown assays coupled with MS, of which HNF4G and PAX6 were validated and compared for their binding to the same promoter sites in the two cell lines. Our studies suggest distinctive proteomic factors associated with the MACC1 promoter in colon cells with different metastatic potential. The dynamic regulatory factors accumulated at the promoter of MACC1 may provide novel insights into the regulatory mechanisms of MACC1 transcription.

A case series of patients with gonadal dysgenesis-associated mixed malignant ovarian germ cell tumor.

Introduction: Malignant germ cell tumors (MGCT) can occur in both genders. In this study, we present eight cases of mixed ovarian MGCT in patients. Most patients reported in the current study are young women, among whom clinical characteristics of gonadal dysgenesis associated MGCT were rarely reported.Methods: Comprehensive information of eight patients with mixed ovarian MGCTs, including patients' age, clinical features, tumor markers, imaging findings, surgical records, pathology, karyotyping tests, chemotherapy and follow-up were collected. Surgical specimens were evaluated by two specialized gynecologic pathologists.Results: All patients received surgery, while seven received chemotherapy. Among them, two received a second surgery and three patients received hormone replacement therapy (HRT) after gonadectomy. Four of five patients with amenorrhea were found to have 46, XY karyotype. All patients showed no sign of recurrence at the latest follow-up.Discussion: Karyotyping or genetics testing in patients with amenorrhea is necessary, especially for patients with pelvic mass, which can help surgeons to evaluate the necessity of gonadectomy before surgery. The patients with gonadal dysgenesis associated mixed ovarian MGCT seem to have better prognosis and long survival time. Thus, HRT, an option that can improve life quality, is worth considering for these patients after gonadectomy.

[Magnetic resonance imaging features of glioma with Brg/Brm associated factor 53a expression].

OBJECTIVE: To explore the magnetic resonance imaging (MRI) characteristics of glioma with Brg/Brm-associated factor 53a (BAF53a) expression.
 Methods: A total of 121 patients with glioma was divided into a BAF53a high expression group (n=79) and a low expression group (n=42) according to the results of immunohistochemistry. Then the MRI characteristics, including lesion location, number, boundary, maximum diameter, peripheral edema, midline structure shift, homogeneity, cystic necrosis, hemorrhage, strengthening degree, ependymal strengthening, pia mater enhancement, deep white matter invasion and lesion across the midline (total 14 items), were analyzed.
 Results: The results showed that there were significance difference in lesion border, lesion edema, enhancement of the lesion, and deep white matter invasion between the 2 groups (all P<0.05).
 Conclusion: The MRI characteristics, such as lesion border, lesion edema degree, enhancement degree of the lesion and deep white matter invasion, might be associated with BAF53a expression in gliomas.

Quantitative proteomic profiling of tumor-associated vascular endothelial cells in colorectal cancer.

To investigate the global proteomic profiles of vascular endothelial cells (VECs) in the tumor microenvironment and antiangiogenic therapy for colorectal cancer (CRC), matched pairs of normal (NVECs) and tumor-associated VECs (TVECs) were purified from CRC tissues by laser capture microdissection and subjected to iTRAQ-based quantitative proteomics analysis. Here, 216 differentially expressed proteins (DEPs) were identified and used for bioinformatics analysis. Interestingly, these proteins were implicated in epithelial mesenchymal transition (EMT), ECM-receptor interaction, focal adhesion, PI3K-Akt signaling pathway, angiogenesis and HIF-1 signaling pathway, which may play important roles in CRC angiogenesis. Among these DEPs we found that Tenascin-C (TNC) was upregulated in TVECs of CRC and correlated with CRC multistage carcinogenesis and metastasis. Furthermore, the reduction of tumor-derived TNC could attenuate human umbilical vein endothelial cell (HUVEC) proliferation, migration and tube formation through ITGB3/FAK/Akt signaling pathway. Based on the present work, we provided a large-scale proteomic profiling of VECs in CRC with quantitative information, a certain number of potential antiangiogenic targets and a novel vision in the angiogenesis bio-mechanism of CRC.

BAF53a is a potential prognostic biomarker and promotes invasion and epithelial-mesenchymal transition of glioma cells.

Increasing evidence indicates that BAF53a is crucial for embryonic development and maintenance of stemness, and may be associated with epithelial-mesenchymal transition (EMT), which suggests its involvement in cancer progression. However, the role of BAF53a in glioma remains unknown. In the present study, BAF53a was found to be highly expressed in glioma tissues and was associated with poor overall survival (OS) and progression-free survival (PFS) in glioma patients. A multivariate Cox regression analysis revealed that BAF53a might be an independent prognostic factor for OS and PFS in glioma patients. Further functional analysis indicated that BAF53a overexpression could promote proliferation and increase the motility and invasion of U87 glioma cells, whereas BAF53a knockdown had the opposite effect. In addition, BAF53a expression was associated with the levels of E­cadherin and vimentin expression in glioma tissues. This was further confirmed in U87 cells expressing different levels of BAF53a; BAF53a overexpression was concomitant with decreased E­cadherin and increased vimentin expression, whereas BAF53a knockdown showed the opposite pattern of expression. Taken together, these results suggest that BAF53a may be a novel prognostic factor for glioma patients, and that BAF53 may facilitate glioma progression by promoting proliferation, invasion, and associate with EMT. Therefore, BAF53a could be a potential promising biomarker and a target for the treatment of glioma.

Loss of plexin-B3 in hepatocellular carcinoma.

Plexins are the primary receptors of semaphorins, and participate in the majority of intracellular pathways triggered by semaphorins, including the regulation of cell adhesion and the motility of numerous cell types. Recently, several studies have reported that plexins can significantly affect different aspects of cancer cell biology, and the aberrant expression of plexins has been observed in a wide variety of tumor types. However, the expression and role of plexin-B3 in hepatocellular carcinoma (HCC) is yet to be investigated. In the present study, plexin-B3 expression was measured in 14 paired HCC samples and the corresponding adjacent non-cancerous tissue by quantitative polymerase chain reaction and western blot analysis. The results indicated that the mRNA and protein expression levels of plexin-B3 were downregulated in HCC samples when compared with the corresponding adjacent non-cancerous tissue. In order to elucidate the correlation between clinicopathological data and the expression of plexin-B3 in patients with HCC, 84 HCC archived specimens were analyzed by immunohistochemistry (IHC). The IHC results revealed that the protein expression level of plexin-B3 was lower in the HCC samples compared with the corresponding adjacent non-cancerous tissue, and plexin-B3 underexpression was correlated with the patient gender and tumor size. In conclusion, these results indicated that loss of plexin-B3 in HCC may be of predictive value for the occurrence and progression of HCC. Thus, plexin-B3 may be a promising biomarker for the diagnosis and treatment of tumors in the future.

MicroRNA-145 inhibits cell proliferation by directly targeting ADAM17 in hepatocellular carcinoma.

MicroRNAs (miRNAs) are key regulators in cell processes. Emerging evidence has suggested that there is a direct association between miRNAs and cancer. However, the exact regulatory mechanisms of miRNAs in tumorigenesis are poorly understood. In the present study, we showed that miR-145 is able to significantly reduce mRNA and protein expression levels of A disintegrin and metalloproteinase 17 (ADAM17) in liver cancer cells (SMMC-7721, BEL-7402 and Huh-7). Dual luciferase reporter assays confirmed that ADAM17 is a direct target of miR-145. Notably, we found that miR-145 inhibits cell proliferation and growth activity in SMMC-7721 cells. These results demonstrated that it may be exert the function of tumor suppression in a particular link of cancer cell growth. Further studies revealed that the silencing of ADAM17 decreased the proliferation and growth activity of SMMC-7721 cells. Moreover, it reduced the expression of MMP-9. In conclusion, miR-145 inhibits liver cancer cell proliferation by directly targeting ADAM17. Thus, it may become a promising biological target in the treatment strategy of hepatocellular carcinoma.

MIR106B and MIR93 prevent removal of bacteria from epithelial cells by disrupting ATG16L1-mediated autophagy.

BACKGROUND & AIMS: Variants in genes that regulate autophagy have been associated with Crohn's disease (CD). Defects in autophagy-mediated removal of pathogenic microbes could contribute to the pathogenesis of CD. We investigated the role of the microRNAs (miRs) MIR106B and MIR93 in induction of autophagy and bacterial clearance in human cell lines and the correlation between MIR106B and autophagy-related gene 16L1 (ATG16L1) expression in tissues from patients with CD. METHODS: We studied the ability of MIR106B and MIR93 to regulate ATG transcripts in human cancer cell lines (HCT116, SW480, HeLa, and U2OS) using luciferase report assays and bioinformatics analyses; MIR106B and MIR93 mimics and antagonists were transfected into cells to modify levels of miRs. Cells were infected with LF82, a CD-associated adherent-invasive strain of Escherichia coli, and monitored by confocal microscopy and for colony-forming units. Colon tissues from 41 healthy subjects (controls), 22 patients with active CD, 16 patients with inactive CD, and 7 patients with chronic inflammation were assessed for levels of MIR106B and ATG16L1 by in situ hybridization and immunohistochemistry. RESULTS: Silencing Dicer1, an essential processor of miRs, increased levels of ATG protein and formation of autophagosomes in cells, indicating that miRs regulate autophagy. Luciferase reporter assays indicated that MIR106B and MIR93 targeted ATG16L1 messenger RNA. MIR106B and MIR93 reduced levels of ATG16L1 and autophagy; these increased after expression of ectopic ATG16L1. In contrast, MIR106B and MIR93 antagonists increased formation of autophagosomes. Levels of MIR106B were increased in intestinal epithelia from patients with active CD, whereas levels of ATG16L1 were reduced compared with controls. Levels of c-Myc were also increased in intestinal epithelia of patients with active CD compared with controls. These alterations could impair removal of CD-associated bacteria by autophagy. CONCLUSIONS: In human cell lines, MIR106B and MIR93 reduce levels of ATG16L1 and autophagy and prevent autophagy-dependent eradication of intracellular bacteria. This process also appears to be altered in colon tissues from patients with active CD.

Evaluation of potential reference genes for qRT-PCR studies in human hepatoma cell lines treated with TNF-α.

In this study, the expression of eight candidate reference genes, B2M, ACTB, GAPDH, HMBS, HPRT1, TBP, UBC, and YWHAZ, was examined to identify optimal reference genes by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis in two human hepatoma cell lines, BEL-7402 and SMMC-7721, treated with tumor necrosis factor-α (TNF-α) for different time periods. The expression stability of these genes was analyzed by three independent algorithms: geNorm, NormFinder, and BestKeeper. Results showed that TBP was the most stably expressed gene in BEL-7402 and SMMC-7721 cell lines under current experimental conditions, and that the optimal set of reference genes required for accurate normalization was TBP and HMBS, based on the pairwise variation value determined with geNorm. UBC and ACTB were ranked as the least stable genes by same algorithms. Our findings provide evidence that using TBP alone or in combination with HMBS as endogenous controls could be a reliable method for normalizing qRT-PCR data in human hepatoma cell lines treated with TNF-α.

Metformin impairs the growth of liver kinase B1-intact cervical cancer cells.

OBJECTIVE: Metformin is one of the most widely used drugs for the treatment of type 2 diabetes. Recent investigations demonstrated that application of metformin reduces cancer risk. The present study aimed to determine the role of liver kinase B1 (LKB1) in the response of cervical cancer cells to metformin. METHODS: LKB1 expression and the integrity of LKB1-AMPK signaling were determined with immunoblot in 6 cervical cancer cell lines. Cellular sensitivity to metformin was analyzed with MTT assay. RESULTS: Metformin inhibited growth of cervical cancer cells, C33A, Me180, and CaSki, but was less effective against HeLa, HT-3, and MS751 cells. Analyzing the expression status and the integrity of LKB1-AMPK-mTOR signaling, we found that cervical cancer cells sensitive to metformin were LKB1 intact and exerted an integral AMPK-mTOR signaling response after the treatment. Ectopic expression of LKB1 with stable transduction system or inducible expression construct in endogenous LKB1 deficient cells improved the activation of AMPK, promoted the inhibition of mTOR, and prompted the sensitivity of cells to metformin. In contrast, knock-down of LKB1 compromised cellular response to metformin. Our further investigation demonstrated that metformin could induce both apoptosis and autophagy in cervical cancer cells when LKB1 is expressed. CONCLUSIONS: Metformin is a potential drug for the treatment of cervical cancers, in particular to those with intact LKB1 expression. Administration of cell metabolism agonists may enhance LKB1 tumor suppression, inhibit cell growth, and reduce tumor cell viability via the activation of LKB1-AMPK signaling.

The effects of hepatitis C virus non-structural protein 3 on cell growth mediated by extracellular signal-related kinase cascades in human hepatocytes in vitro.

Hepatitis C virus (HCV) infection has become a severe health problem worldwide. The viral proteins are believed to be among the most important factors that contribute to HCV mediated pathogenesis. Accumulated evidence demonstrating that HCV non-structural protein 3 (NS3) possesses oncogenic potential, and is involved in the regulation of cell proliferation has been documented. In this study, we emphasized the effect of HCV NS3 protein on cell proliferation in the immortally normal hepatocyte QSG7701 cells. The cell line transfected with plasmid expressing NS3 protein showed enhanced cell growth, extracellular signal-related kinase (ERK) activation, DNA binding activities of transcription factors of activator protein 1 (AP-1) and NF-kappaB, and cyclin D1 overexpression, but without activation of Jun amino-terminal kinase or p38. Pre-treatment of NS3 protein expressing cells with ERK inhibitor, PD98059, blocked the activation of AP-1 and NF-kappaB, and inhibited cyclin D1 expression and cell proliferation. The results suggest that NS3-mediated cell growth occurs through activation of ERK/AP-1 and NF-kappaB/cyclin D1 cascades.

Novel amino-modified silica nanoparticles as efficient vector for hepatocellular carcinoma gene therapy.

Due to the ineffective conventional treatment for hepatocellular carcinoma (HCC), the nonviral gene delivery system has been proved to be an attractive alternative to HCC therapy. In this work, we have developed a kind of new self-assembled nanoparticles, which were named as amino-modified silica nanoparticles (AMSNs). Scanning electron microscopy and zeta potential results demonstrated that AMSNs had a diameter of 20-30 nm and positive surface charges of +11.3 mV, respectively. The AMSNs could bind DNA strongly and protect DNA from degradation, which was confirmed by DNA-binding assay and serum protection assay. Furthermore, AMSNs could transfer foreign DNA into targeted cells with high transfection efficiency and little cytotoxicity. Combined with the p53 gene, AMSNs could transfect pp53-EGFP in HepG2 cells and result in a high-level of p53 mRNA and protein expressions. The nude mice treated with AMSNs/pp53-EGFP complexes showed significant tumor growth inhibition. Our results showed the AMSNs, an efficient gene vector, had the potential of gene therapy for HCC.

Specific activation of 2'-5'oligoadenylate synthetase gene promoter by hepatitis C virus-core protein: a potential for developing hepatitis C virus targeting gene therapy.

AIM: To examine whether 2'-5'oligoadenylate synthetase (OAS) gene promoter can be specifically activated by hepatitis C virus (HCV)-core protein. METHODS: Human embryo hepatic cell line L02 was transfected with pcDNA3.1-core plasmid and selected by G418. Expression of HCV-core was detected by reverse transcription polymerase chain reaction and Western blotting. The OAS promoter sequence was amplified from the genomic DNA and inserted into pGL3-basic vector. The resultant pGL3-OAS-Luci plasmid was transiently transfected into L02/core cells and luciferase activity was assayed. RESULTS: L02/core cell line stably expressing HCV-core protein was established. The pGL3-OAS-Luci construct exhibited significant transcriptional activity in the L02/core cells but not in the L02 cells. CONCLUSION: HCV-core protein activates the OAS gene promoter specifically and effectively. Utilization of OAS gene promoter would be an ideal strategy for developing HCV-specific gene therapy.