[Correlation of CpG methylation status of Runx3 with pathogenesis of gastric carcinoma].

OBJECTIVE: To investigate the role of Runx3 gene CpG island methylation in the development of human gastric carcinoma. METHODS: A total of 150 tumor specimens from patients with gastric carcinoma and 50 normal tissue specimens were selected. Methylation specific PCR (MSP) and pyrosequencing (PS) were used to detect the methylation status of Runx3 gene promoter. RESULTS: Compared to normal tissue samples, a significant increase of CpG island methylation status of Runx3 gene was observed in gastric carcinomas (MSP: 67.3% vs. 40.0%, P = 0.002; PS: 76.0% vs. 30.0%, P < 0.01). Runx3 gene methylation was only related to tumor size (P < 0.05) based on MSP analysis. PS test however showed that the extent of methylation of Runx3 gene was related to the tumor size (P = 0.004), Lauren's classification (P = 0.043), depth of invasion (P < 0.01), lymph node metastasis (P = 0.021) and TNM staging (P = 0.045). CONCLUSIONS: Methylation status of Runx3 gene detectable by PS is closely correlated with clinicopathological parameters of gastric carcinoma, including tumor size, Lauren's classification, depth of invasion, lymph node metastasis and TNM staging. PS is more sensitive than MSP in the detection of Runx3 gene methylation, which may serve as an important marker for early diagnosis and treatment of gastric carcinoma.

Small biomarkers with massive impacts: PI3K/AKT/mTOR signalling and microRNA crosstalk regulate nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumours of the head and neck in Southeast Asia and southern China. The Phosphatidylinositol 3-kinase/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signalling pathway is involved in processes related to tumour initiation/progression, such as proliferation, apoptosis, metastasis, and drug resistance, and is closely related to the clinicopathological features of NPC. In addition, key genes involved in the PI3K/AKT/mTOR signalling pathway undergo many changes in NPC. More interestingly, a growing body of evidence suggests an interaction between this signalling pathway and microRNAs (miRNAs), a class of small noncoding RNAs. Therefore, in this review, we discuss the interactions between key components of the PI3K/AKT/mTOR signalling pathway and various miRNAs and their importance in NPC pathology and explore potential diagnostic biomarkers and therapeutic targets.

Cross-link between ferroptosis and nasopharyngeal carcinoma: New approach to radiotherapy sensitization.

Ferroptosis is a recently discovered special type of regulated cell death that is strongly associated with both homeostasis maintenance and cancer development. Previous studies have indicated that a number of small-molecular agents inducing ferroptosis have great potential in the treatment of different types of cancer, including breast, pancreatic, prostate and head and neck cancer. However, the role of ferroptosis in nasopharyngeal carcinoma (NPC) has remained to be fully determined. To the best of our knowledge, no review of the currently available studies on this subject has been published to date. The metabolism and expression of specific genes that regulate ferroptosis may represent a promising radiosensitization target in cancer treatment. The aim of the present review was to describe the cross-link between ferroptosis and NPC and to discuss the potential value of regulators and the possible mechanism underlying the role of ferroptosis in the radiosensitization of NPC, in the hope that linking the mechanism of ferroptosis with the development of NPC will accelerate the development of novel ferroptosis-based targets and radiotherapy strategies in NPC.

The Role of Autophagy in Cancer Radiotherapy.

BACKGROUND: Autophagy, a pathway for lysosomal-mediated cellular degradation, is a catabolic process that recycles intracellular components to maintain metabolism and survival. It is classified into three major types: macroautophagy, microautophagy, and the chaperone-mediated autophagy (CMA). Autophagy is a dynamic and multistep process that includes four stages: nucleation, elongation, autophagosome formation, and fusion. Interestingly, the influence of autophagy in cancer development is complex and paradoxical, suppressive, or promotive in different contexts. Autophagy in cancer has been demonstrated to serve as both a tumour suppressor and promoter. Radiotherapy is a powerful and common strategy for many different types of cancer and can induce autophagy, which has been shown to modulate sensitivity of cancer to radiotherapy. However, the role of autophagy in radiation treatment is controversial. Some reports showed that the upregulation of autophagy was cytoprotective for cancer cells. Others, in contrast, showed that the induction of autophagy was advantageous. Here, we reviewed recent studies and attempted to discuss the various aspects of autophagy in response to radiotherapy of cancer. Thus, we could decrease the viability of cancer cell and increase the sensibility of cancer cells to radiation, providing a new basis for the application of autophagy in clinical tumor radiotherapy.

Carboxyl terminal activating region 3 of latent membrane protein 1 encoded by the Epstein­Barr virus regulates cell proliferation and protein expression in NP69 cells.

In the present study, the mechanism by which carboxyl terminal activating region 3 (CTAR3) of latent membrane protein 1 (LMP1), encoded by the Epstein­Barr virus, regulated cell proliferation and protein expression was investigated in the nasopharyngeal epithelial cell line NP69. The deletion mutant LMP1 (LMP1Δ232­351; amino acid residues including 232­351 codons in CTAR3 deleted) was generated by polymerase chain reaction. An NP69­LMP1Δ232­351 cell line was established by retroviral infection. Finally, cell proliferation and protein expression of NP69 cells expressing LMP1Δ232­351 were examined using a cell growth curve and western blot analysis. The results demonstrated: i) The proliferation of NP69­LMP1Δ232­351 cells was significantly decreased compared with cells expressing wild type LMP1 (LMP1WT; n=3; P<0.05); ii) 17 proteins exhibited differential protein expression (>2­fold change) in NP69­LMP1Δ232­351 cells compared with NP69­LMP1WT cells; and iii) LMP1WT was involved in activating the Janus kinase 3 (JAK3) promoter and regulating the expression of JAK3 protein, while LMP1Δ232­351 was almost defective in ability to activate the JAK promoter. These results suggested that LMP1­CTAR3 may be an important functional domain for regulating cell proliferation and protein expression in nasopharyngeal epithelial cells.

LncRNA LUCRC Regulates Colorectal Cancer Cell Growth and Tumorigenesis by Targeting Endoplasmic Reticulum Stress Response.

Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide, and is well known for its strong invasiveness, rapid recurrence, and poor prognosis. Long non-coding RNAs (lncRNAs) have been shown to be involved in the development of various types of cancers, including colorectal cancer. Here, through transcriptomic analysis and functional screening, we reported that lncRNA LUCRC (LncRNA Upregulated in Colorectal Cancer) is highly expressed in colorectal tumor samples and is required for colorectal cancer cell proliferation, migration, and invasion in cultured cells and tumorigenesis in xenografts. LUCRC was found to regulate target gene expression of unfolded protein response (UPR) in endoplasmic reticulum (ER), such as BIP. The clinical significance of LUCRC is underscored by the specific presence of LUCRC in blood plasma of patients with colorectal cancers. These findings revealed a critical regulator of colorectal cancer development, which might serve as a therapeutic target in colorectal cancer.

Investigation of transcriptional gene silencing and mechanism induced by shRNAs targeted to RUNX3 in vitro.

AIM: To investigate transcriptional gene silencing induced by short hairpin RNAs (shRNAs) that target gene prompter regions of RUNX3 gene, and whether shRNAs homologous to DNA sequences may serve as initiators for methylation. METHODS: According to the principle of RNAi design, pSilencer3.1-H1-shRNA/RUNX3 expression vector was constructed, The recombinant plasmid shRNA was transfected into human stomach carcinoma cell line SGC7901 with Lipofectamine 2000. Then, the positive cell clones were screened by G418. The mRNA and protein expression level of RUNX3 in the stable transfected cell line SGC7901 were determined by RT-PCR, Western blotting and immunocytochemistry. Characteristics of the cell lines including SGC7901, pSilencer3.1-H1/SGC7901 and pSilencer3.1-H1-shRNA/RUNX3/SGC7901 were analyzed with growth curves, clone formation rate and cell-cycle distribution. The activated level of RUNX3 was examined after treatment with the different density of 5'-aza-2'-deoxycytidine (5-Aza-CdR) by using semi-quantitative RT-PCR and Western blotting. RESULTS: In the cell line SGC7901 transfected with pSilencer3.1-H1-shRNA/RUNX3, mRNA and protein expression of the RUNX3 gene was lost identified by RT-PCR, Western blotting and immunocytochemistry assay. The growth of pSilencer3.1-H1-shRNA/ RUNX3/SGC7901 cells without expression of RUNX3 was the fastest (P < 0.05), its rate of clone formation was the highest (P < 0.01), and the cell distribution in G(0)/G(1) and S/M phases was lowest and highest, respectively (P < 0.05), compared with that of the transfected pSilencer3.1-H1 and non-transfected cells. Through RT-PCR and Western blot assay, inactivated RUNX3 could not be reactivated by 5-Aza-CdR. CONCLUSION: We found that, although shRNAs targeted to gene prompter regions of RUNX3 could effectively induce transcriptional repression with chromatic changes characteristic of inaction promoters, this was independent of DNA methylation, and the presence of RNA-dependent transcriptional silencing showed that RNA-directed DNA methylation might be an existing gene regulatory mechanism relative to the methylated in humans.

The tumor supressor function of STGC3 and its reduced expression in nasopharyngeal carcinoma.

STGC3 is a novel candidate tumor suppressor gene that was found to be associated with nasopharyngeal carcinoma (NPC) via the cDNA cloning and RACE processes. The biological function of the STGC3 protein and its expression level in nasopharyngeal carcinoma remain unknown. This study aimed to evaluate the STGC3 protein expression level in NPC and to investigate the inhibitory function of STGC3 as a candidate tumor suppressor gene. We assessed the expression of the STGC3 protein in NPC biopsies and normal control specimens via Western blot and immunohistochemical analysis. The expression of STGC3 as induced by doxycycline (Dox) via a tetracycline (Tet)-regulated system in human nasopharyngeal carcinoma cell line CNE2 was also established, and the effect of STGC3 restoration on the biological behavior of CNE2 was observed. A reduced level of STGC3 expression (0.978 +/- 0.213 versus 0.324 +/- 0.185, P < 0.05) was detected in NPC versus normal nasopharyngeal tissue by Western blot assay. Immunohistochemical assays for STGC3 detected positive staining in the nuclei and cytoplasm of epithelial cells, and the positive expression rate in NPC, 8 of 21 (38%), was lower than that in normal nasopharynx samples, 16 of 22 (72%). After STGC3 expression was restored, the growth capacity and clone formation potential of CNE2 cells in soft agar were significantly suppressed, and the cell percentage in G(0)/G(1) phase increased, while the percentage of cells entering the S and G(2) phases decreased. This indicates that an abnormality in STGC3 expression is associated with nasopharyngeal carcinogenesis and that it may play an important role in controlling cell growth and regulating the cell cycle.

Expression of p16 gene and Rb protein in gastric carcinoma and their clinicopathological significance.

AIM: To analyze the correlation between the protein expression of p16 and Rb genes in gastric carcinoma (GC), to investigate the role of p16 gene in invasion and lymph node metastasis of GC, and to examine the deletion and mutation in exon 2 of p16 gene in GC. METHODS: The protein expression of p16 and Rb genes was examined by streptavidin-peroxidase conjugated method (S-P) in normal gastric mucosa, dysplastic gastric mucosa and GC. The deletion and mutation of p16 gene were examined by polymerase chain reaction (PCR) and polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) respectively in normal gastric mucosa and GC. RESULTS: The positive rates of P16 and Rb protein expression respectively were 96% (77/80) and 99% (79/80) in normal gastric mucosa, 92% (45/50) and 80% (40/50) in dysplastic gastric mucosa, 48% (58/122) and 60% (73/122) in GC. The positive rates of P16 and Rb protein expression in GC were significantly lower than that in normal gastric mucosa and dysplastic gastric mucosa (P<0.05). The positive rate of P16 protein expression in mucoid carcinoma (10%, 1/10) was significantly lower than that in poorly differentiated carcinoma (51%, 21/41), undifferentiated carcinoma (58%, 15/26) and signet ring cell carcinoma (62%, 10/16) (P<0.05). The positive rates of P16 protein in 30 cases of paired primary and lymph node metastatic GC were 47% (14/30) and 17% (5/30) respectively, being significantly lower in the later than in the former (P<0.05). There was no mutation in exon 2 of p16 gene in the 25 freshly resected primary GCs. But five cases in the 25 freshly resected primary GCs displayed deletion in exon 2 of p16 gene. The positive rate of both P16 and Rb proteins was 16% (14/90), and the negative rate of both P16 and Rb proteins was 8% (7/90) in 90 GCs. The rate of positive P16 protein with negative Rb protein was 33% (30/90). The rate of negative P16 protein with positive Rb protein was 43% (39/90). There was reverse correlation between P16 and Rb expression in 90 GCs (P<0.05). CONCLUSION: The loss protein expression of p16 and Rb genes is related to GC. The loss expression of P16 protein is related to the histopathologic subtypes and lymph node metastasis of GC. Expression of P16 and Rb proteins in GC is reversely correlated. The deletion but not mutation in exon 2 of p16 gene may be involved in GC.

Expression of p21(WAF1) and p53 and polymorphism of p21(WAF1) gene in gastric carcinoma.

AIM: To investigate the relationship between expression of p21(WAF1) and p53 gene, and to evaluate the deletion and polymorphism of p21(WAF1) gene in gastric carcinoma (GC). METHODS: Expression of p21 and p53 proteins, and deletion and polymorphism of p21 gene in GC were examined by streptavidin-peroxidase conjugated method (SP) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) respectively. RESULTS: The expression of p21 and p53 was found in 100% (20/20) and 0% (0/20) of normal gastric mucosae(NGM), 92.5% (37/40) and 15.0% (6/40) of dysplasia (DP) and 39.8% (43/108) and 56.5% (61/108) of GC, respectively. The positive rate of p21 in GC was lower than that in NGM and DP (P<0.05), while the positive rate of p53 in GC was higher than that in NGM and DP (P<0.05). p21 and p53 were significantly expressed in 63.3% (19/30) and 36.7% (11/30), 35.0% (14/40) and 77.5% (31/40), 26.7% (4/15) and 80.0% (12/15), 30.8% (4/13) and 30.8% (4/13), and 20.0% (2/10) and 30.0% (3/10) of well-differentiated, poorly-differentiated, undifferentiated carcinomas, mucoid carcinomas and signet ring cell carcinomas. The expression of p21 in well-differentiated carcinomas was significantly higher than that in poorly-differentiated, un-differentiated, mucoid carcinomas and signet ring cell carcinomas (P<0.05). Contrarily, The expression of p53 was increased from well-differentiated to poorly-differentiated and un-differentiated carcinomas (P<0.05). The expression of p21 and p53 in paired primary and metastatic GC (35.3% and 70.6%) was different from non-metastatic GC (62.5% and 42.5%) markedly (P<0.05). The expression of p21 in invasive superficial muscle (60.0%) was higher than that in invasive deep muscle or total layer (35.2%) (P<0.05) and was higher in TNM stages I (60.0%) and II (56.2%) than in stages III (27.9%) and IV (22.2%) (P<0.05), whereas the expression of p53 did not correlate to invasion depth or TNM staging (P>0.05). The exoression patterns of p53+/p21-, and of p53-/p21+ were found in 5.0% and 82.5% of DP. There was a significant correlation between expression of p21 and p53 (P<0.05). But there was no significant correlation between expression of both in GC (P>0.05). There was no deletion in exon 2 of p21 gene in 30 cases of GC and 45 cases of non-GC, but polymorphism of p21 gene at exon 2 was found in 26.7% (8/30) of GC and 8.9% (4/45) of non-GC, a significant difference was found between GC and non-GC (P<0.05). There was no significant relation between p21 expression of polymorphism (37.5%, 3/8) and non-polymorphism (45.5%, 10/22) in GC (P>0.05). CONCLUSION: The loss of p21 protein and abnormal expression of p53 are related to carcinogenesis, differentiation and metastasis of GC. The expression of p21 is related to invasion and clinical staging in GC intimately. The expression of p21 protein depends on p53 protein largely in NGM and DP, but not in GC. No deletion of p21 gene in exon 2 can be found in GC. The polymorphism of p21 gene might be involved in gastric carcinogenesis.There is no significant association between polymorphism of p21 gene and expression of p21 protein.

Involvement of EBV-encoded BART-miRNAs and dysregulated cellular miRNAs in nasopharyngeal carcinoma genesis.

The definite molecular mechanisms underlying the genesis of nasopharyngeal carcinomas (NPCs) remain to be completely elucidated. miRNAs are small non-coding RNAs which are implicated in cell proliferation, apoptosis, and even carcinogenesis through negatively regulating gene expression post-transcriptionally. EBV was the first human virus found to express miRNAs. EBV-encoded BART-miRNAs and dysregulated cellular miRNAs are involved in carcinogenesis of NPC by interfering in the expression of viral and host cell genes related to immune responses and perturbing signal pathways of proliferation, apoptosis, invasion, metastasis and even radio-chemo-therapy sensitivity. Additional studies on the roles of EBV-encoded miRNAs and cellular miRNAs will provide new insights concerning the complicated gene regulated network and shed light on novel strategies for the diagnosis, therapy and prognosis of NPC.

STGC3 inhibits xenograft tumor growth of nasopharyngeal carcinoma cells by altering the expression of proteins associated with apoptosis.

STGC3 is a potential tumor suppressor that inhibits the growth of the nasopharyngeal carcinoma cell line CNE2; the expression of this protein is reduced in nasopharyngeal carcinoma compared with normal nasopharyngeal tissue. In this study, we investigated the tumor-suppressing activity of STGC3 in nude mice injected subcutaneously with Tet/pTRE-STGC3/CNE2 cells. STGC3 expression was induced by the intraperitoneal injection of doxycycline (Dox). The volume mean of Tet/pTRE-STGC3/CNE2+Dox xenografts was smaller than that of Tet/pTRE/CNE2+Dox xenografts. In addition, Tet/pTRE-STGC3/CNE2+Dox xenografts showed an increase in the percentage of apoptotic cells, a decrease in Bcl-2 protein expression and an increase in Bax protein expression. A proteomic approach was used to assess the protein expression profile associated with STGC3-mediated apoptosis. Western blotting confirmed the differential up-regulation of prohibitin seen in proteomic analysis. These results indicate that overexpression of STGC3 inhibits xenograft growth in nude mice by enhancing apoptotic cell death through altered expression of apoptosis-related proteins such as Bcl-2, Bax and prohibitin. These data contribute to our understanding of the function of STGC3 in human nasopharyngeal carcinoma and provide new clues for investigating other STGC3-associated tumors.

STGC3 inhibits xenograft tumor growth of nasopharyngeal carcinoma cells by altering the expression of proteins associated with apoptosis

STGC3 is a potential tumor suppressor that inhibits the growth of the nasopharyngeal carcinoma cell line CNE2; the expression of this protein is reduced in nasopharyngeal carcinoma compared with normal nasopharyngeal tissue. In this study, we investigated the tumor-suppressing activity of STGC3 in nude mice injected subcutaneously with Tet/pTRE-STGC3/CNE2 cells. STGC3 expression was induced by the intraperitoneal injection of doxycycline (Dox). The volume mean of Tet/pTRE-STGC3/CNE2+Dox xenografts was smaller than that of Tet/pTRE/CNE2+Dox xenografts. In addition, Tet/pTRE-STGC3/CNE2+Dox xenografts showed an increase in the percentage of apoptotic cells, a decrease in Bcl-2 protein expression and an increase in Bax protein expression. A proteomic approach was used to assess the protein expression profile associated with STGC3-mediated apoptosis. Western blotting confirmed the differential up-regulation of prohibitin seen in proteomic analysis. These results indicate that overexpression of STGC3 inhibits xenograft growth in nude mice by enhancing apoptotic cell death through altered expression of apoptosis-related proteins such as Bcl-2, Bax and prohibitin. These data contribute to our understanding of the function of STGC3 in human nasopharyngeal carcinoma and provide new clues for investigating other STGC3-associated tumors.

[Expression and structure of BNIP3L in lung cancer].

BACKGROUND & OBJECTIVE: Bcl-2/E1B 19kDa interacting protein3-like (BNIP3L) gene is a tumor suppressor gene cloned from a human fetal liver cDNA library, which is located at 8p21, one of the high frequent regions of loss of heterozygosity (LOH) in lung carcinoma. BNIP3L protein can interact with antiapoptotic proteins, such as Bcl-2, Bcl-x(L), E1B19K, which promotes apoptosis. This study was designed to explore the correlation of alteration of expression and structure of BNIP3L gene with the progression of lung cancer. METHODS: The expression and structure of BNIP3L gene in 4 lung cancer cell strains and 30 tissues were determined by SP immunohistochemistry, immunoblot, semi-quantitative reverse transcription-PCR (RT-PCR), PCR-single strain conformation polymorphism (PCR-SSCP). RESULTS: (1) In 4 lung cancer cell strains, BNIP3L protein was not detected in A549, NCI-H460, NCI-H446, except for NCI-H520, in which the protein expression level was slightly lower than that in immortal bronchial epithelial cell strain HBE4-E6/E7. BNIP3L protein was observed in 46.7% (14/30) lung cancer tissues, while 100% (12/12) in normal lung tissues. The difference was significant in statistics (P< 0.05). (2) BNIP3L mRNA was detected in 4 lung cancer cell strains; and there existed no obvious discrepancy of the amount between these cell strains and HBE4-E6/E7. Absence or decrease of BNIP3L mRNA was observed in 26.7%(8/30) of lung cancer tissues. The average quantity of BNIP3L mRNA was 0.404+/-0.070 in lung cancer tissues, while 0.575+/-0.065 in paired normal lung tissues. The difference was significant in statistics (P< 0.05). In all the cancerous cell strains and tissues with BNIP3L mRNA, the products of RT-PCR were as long as those from their control samples in size, including the entire coding region, and no variation of BNIP3L gene structure such as absence, rearrangement, aberrant splicing were detected.(3) No point mutation was detected in all 6 exons of BNIP3L gene in 4 lung cancer cell strains and 30 tissues. CONCLUSION: BNIP3L protein expression was down-regulated in lung cancer, which might be involved in the occurrence and/or development of lung cancer. The down-regulation of BNIP3L protein expression in lung cancer was partly caused by the down-regulation of its transcription. The variation of gene structure may be not the reason of BNIP3L inactivity in lung cancer.

[Identification of down-regulated expressed sequence tag at chromosome 3p21 in nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: It was reported that a locus of high frequency loss of heterozygosity was found at 3p14-25 of nasopharyngeal carcinoma (NPC) cells. This study was designed to identify the expressed sequence tags (ESTs) associated with NPC at chromosome 3p21 in order to clone new candidate NPC-associated genes at the locus. METHODS: The expression of relative ESTs at 3p21 was determined in nasopharyngeal carcinoma tissues and normal nasopharyngeal epithelia using ESTs homology analysis with bioinformatics in computer network combined with reverse transcription-polymerase chain reaction (RT-PCR). The expression of EST was detected in other normal tissues and tumor cell lines using Northern blot analysis. RESULTS: Comparing with expression of normal nasopharyngeal epithelia, EST (N31985) was down-regulated in 60.00% (3/5) nasopharyngeal carcinoma cell lines and 47.06% (16/34) nasopharyngeal carcinoma tissues (P < 0.05). CONCLUSION: N31985 is down-regulated in NPC, suggesting it may play a role in NPC carcinogenesis.

[Molecular cloning and functional analysis of STGC3 - a novel gene on chromosome 3p21].

BACKGROUND & OBJECTIVE: A locus of loss of heterozygosity (LOH) with high frequency has been found on chromosome 3p21 in nasopharyngeal carcinoma (NPC). On the basis of our former research, this study was designed to clone and analyze a novel NPC-associated gene at this locus. METHODS: The full-length cDNA sequence of this gene was obtained by plasmid cDNA sequencing and RACE,and analyzed by bioinformatics. The pEGFP-C2/STGC3 fusion mammalian expression vector was constructed, and transfected into COS7 and CNE2 cell lines mediated by lipofectin to analyze the subcellular localization of gene expressing proteins. The expression of STGC3 was detected in normal tissues and tumor cell lines by Northern blot. RESULTS: An 1 271 bp full-length cDNA sequence of gene,which had no obvious homology with other known genes in bioinformatic databases,was obtained. This gene,named STGC3 (GenBank accession number:AY078383), localized on chromosome 3p21, and encodes a protein consisting of 146 amino acids. Protein localization analysis under fluorescent microscope indicated that STGC3 fusion protein was distributed in nucleus and cytoplasm 24-48 hours after transfection. MTE(TM)Array2 Northern blot analysis showed STGC3 expressed in both normal tissues and tumor cells,while its expression down-regulated in many tumor cell lines, such as Burkitt's lymphoma cell line Daudi. CONCLUSIONS: STGC3 is a novel gene, and down-regulated in NPC and many other tumor cell lines. STGC3 fusion protein distributes in cytoplasm and nucleus.

Effect of apolipoprotein A-I on ATP binding cassette transporter A1 degradation and cholesterol efflux in THP-1 macrophage-derived foam cells.

Cholesterol-loaded macrophage foam cells are a central component of atherosclerotic lesions. ATP binding cassette transporter A1 (ABCA1), the defective molecule in Tangier disease, mediates the efflux of phospholipid and cholesterol from cells to apolipoprotein A-I (apoA-I), reversing foam cell formation. This study investigated the effect of apoA-I on ABCA1 degradation and cholesterol efflux in THP-1 macrophage-derived foam cells. After exposure of the cultured THP-1 macrophage-derived foam cells to apoA-I for different time, cholesterol efflux, ABCA1 mRNA and protein levels were determined by FJ-2107P type liquid scintillator, RT-PCR and Western blot, respectively. The mean ABCA1 fluorescence intensity on THP-1 macrophage-derived foam cells was detected by flow cytometry. Results showed that apoA-I markedly increased ABCA1-mediated cholesterol efflux from THP-1 macrophage-derived foam cells. This was accompanied by an increase in the content of ABCA1. ApoA-I did not alter ABCA1 mRNA abundance. Significantly, thiol protease inhibitors increased the level of ABCA1 protein and slowed its decay in THP-1 macrophage-derived foam cells, whereas none of the proteosome-specific inhibitor lactacystin, other protease inhibitors, or the lysosomal inhibitor NH4Cl showed such effects. The apoA-I-mediated cellular cholesterol efflux was enhanced by thiol protease inhibitors. Our results suggested that thiol protease inhibitors might provide an alternative way to upregulate ABCA1 protein. This strategy is especially appealing since it may mimic the stabilizing effect of the natural ligands apoA-I.