Long-chain polyunsaturated fatty acids influence colorectal cancer progression via the interactions between the intestinal microflora and the macrophages.

The metabolism of long-chain polyunsaturated fatty acids (LCPUFAs) is closely associated with the risk and progression of colorectal cancer (CRC). This paper aims to investigate the role of LCPUFA in the crosstalk between intestinal microflora and macrophages, as well as the effects of these three parties on the progression of CRC. The metabolism and function of LCPUFA play important roles in regulating the composition of the human gut microflora and participating in the regulation of inflammation, ultimately affecting macrophage function and polarization, which is crucial in the tumor microenvironment. The effects of LCPUFA on cellular interactions between the two species can ultimately influence the progression of CRC. In this review, we explore the molecular mechanisms and clinical applications of LCPUFA in the interactions between intestinal microflora and intestinal macrophages, as well as its significance for CRC progression. Furthermore, we reveal the role of LCPUFA in the construction of the CRC microenvironment and explore the key nodes of the interactions between intestinal flora and intestinal macrophages in the environment. It provides potential targets for the metabolic diagnosis and treatment of CRC.

Iron, Copper, and Zinc Homeostasis in the Battle between Macrophage and Mycobacterium Tuberculosis.

Iron, copper, and zinc play integral roles in the battle against Mycobacterium tuberculosis (Mtb) infection; however, they are often trapped between nutrients and toxins, posing a significant challenge to macrophages and Mtb to utilize them. Due to this two-sided effect, macrophages and Mtb strictly regulate metal uptake, storage, and excretion. This review discusses the balanced regulation of iron, copper, and zinc in macrophages and Mtb during infection, focusing on the intracellular metal regulatory system. Macrophages typically use the two-sided effect of metals to limit Mtb access to nutrients or poison them. Mtb has developed a metal metabolism regulatory mechanism compatible with the nutritional immune strategy. This includes the mediation of relevant metalloproteins and metalloenzymes to maintain the multimetal balance. This review also explored the regulation of metal metabolism homeostasis in macrophages resistant to Mtb infection, providing a theoretical foundation for identifying potential clinical targets for Mtb infection, developing metalloid anti-tuberculosis drugs, and understanding the immune mechanisms against intracellular Mtb infection.

Role of Exosomal Non-Coding RNA in the Tumour Microenvironment of Genitourinary System Tumours.

In recent years, genitourinary system tumors are common in people of all ages, seriously affecting the quality of life of patients, the pathogenesis and treatment of these diseases are constantly being updated and improved. Exosomes, with a lipid bilayer that enable delivery of their contents into body fluids or other cells. Exosomes can regulate the tumor microenvironment, and play an important role in tumor development. In turn, cellular and non-cellular components of tumor microenvironment also affect the occurrence, progression, invasion and metastasis of tumor. Non-coding RNAs have been shown to be able to be ingested and released by exosomes, and are seen as a potential tool in cancer diagnosis and treatment. Here, we summarize the effect of non-coding RNAs of exosome contents on the tumor microenvironment of genitourinary system tumor, expound the significance of non-coding RNAs of exosome in the occurrence, development, diagnosis and treatment of cancers.

Message in hand: the application of CRISPRi, RNAi, and LncRNA in adenocarcinoma.

Gene editing interference technology has been flourishing for more than 30 years. It has always been a common means to interfere with the expression of particular genes. Today it has shown a broad application prospect in clinical treatment, especially in adenocarcinoma treatment. In just a few years, the CRISPRi technology has attracted much z attention with its precise targeting and convenient operability significantly promoted the transformation from bench to bedside, and won the Nobel Prize in Chemistry 2020. In recent years, the importance of non-coding RNA has led LncRNA research to the center. At the same time, it also recalls the surprises obtained in laboratory and clinic research by RNAi technologies such as microRNA, siRNA, and shRNA at the beginning of the century. Therefore, this article focuses on CRISPRi, RNAi, and LncRNA to review their gene interference mechanisms currently expected to be translational research. Their applications and differences in adenocarcinoma research will also be described powerfully. It will provide a helpful reference for scientists to understand better and apply several RNA interference technologies.

Positive Correlative over-Expression between eIF4E and Snail in Nasopharyngeal Carcinoma Promotes its Metastasis and Resistance to Cisplatin.

EIF4E is the rate-limiting factor in the mRNA translation of specific set of oncogenes. Snail is the core transcription factor of epithelial-mesenchymal transition (EMT), a key step of cancer metastasis. The connection between the two oncoproteins has not been well established in the human cancer tissues and in nasopharyngeal carcinoma (NPC). Here we showed that the positive correlative over-expression was seen between eIF4E and Snail in NPC tissues, and the expression was significantly higher in the metastatic NPC than in the un-metastatic NPC. In NPC cells, eIF4E knockdown significantly reduced Snail mRNA and protein levels, increased the mRNA level of E-cad (a direct downstream gene of Snail and a negative EMT marker), attenuated the invasive ability of the cells, and sensitized the cells to cisplatin in invasion. In contrast, enforced the expression of eIF4E significantly increased Snail mRNA and protein levels, and promoted the invasive ability in NPC cells. Under the condition of the high eIF4E expression, Snail knockdown significantly increased E-cad mRNA level and weaken the invasive ability of NPC cells. Finally, eIF4E directly bound Snail mRNA for translation initiation displayed by the RIP assay. Therefore, the results firstly suggested that eIF4E enhanced the Snail expression in both transcription and translation manner in human cancer tissues and targeting the eIF4E/Snail axis might intervene with the EMT and metastasis of NPC. This finding provided a new clue for further understanding the metastatic mechanism of human cancers and for preventing and treating NPC metastasis.

Inhibition of human cervical cancer cell invasion by IL-37 involving runt related transcription factor 2 suppression.

BACKGROUND: IL-37 is a newly anti-inflammatory cytokine whose function is largely unknown in cancer. Our preliminary experiment found IL-37 could inhibit the invasion of human cervical cancer (CC) cells and influence the expression of RUNX family whose function was also unclear in CC. The present study aims to further investigate the effects of IL-37 on cell invasion and runt related transcription factor 2 (RUNX2) expression in CC cell lines. METHODS: Firstly, plasmid overexpressing IL-37 or RUNX2 was transfected into Siha and C33A cells by Hilymax. Then, the effects of IL-37 on the mRNA expression of RUNX1, RUNX2 and RUNX3 gene were detected by quantitative real-time polymerase chain reaction. Protein expression was measured by Western blot and the grayscale scanning analysis. Finally, the effects of IL-37 or RUNX2 on cell invasion were tested by transwell assay. RESULTS: IL-37 inhibited the mRNA expression of RUNX1 and RUNX2, and increased that of RUNX3 in CC cells. Among the three RUNX genes, RUNX2 showed the most significant change in mRNA expression (decreased by78.5% in Siha cells and by 61.5% in C33A cells) and thus was chosen for the following study. Overexpressed IL-37 inhibited cell invasion by 36.23% in Siha cells (P<0.05) and 26.21% in C33A cells (P<0.01). Overexpression of RUNX2 promoted cell invasion. Up-regulation of IL-37 suppressed markedly the mRNA and protein expression of RUNX2. Furthermore, overexpressed RUNX2 partially restored the inhibited cell invasion by IL-37 to 86.62% in Siha cells (P<0.01) and 87.08% in C33A cells (P<0.01). CONCLUSIONS: IL-37 can significantly inhibit the cell invasion of Siha and C33A cells, which involves the suppression of RUNX2.

Y Box-Binding Protein 1 Promotes Epithelial-Mesenchymal Transition, Invasion, and Metastasis of Cervical Cancer via Enhancing the Expressions of Snail.

OBJECTIVE: Y box-binding protein 1 (YB-1) is a potent oncogenic protein. How it regulates Snail in most tumors including cervical cancer is unknown. This article is to study if YB-1 plays a role in cervical cancer via regulating the expression of Snail. METHODS: Immunohistochemical staining of YB-1, Snail, and E-cadherin (E-cad) was performed on tissue specimens including 35 cases of chronic cervicitis (as a control), 35 cases of cervical intraepithelial neoplasm (CIN) I, 35 cases of CIN II/III, 28 cases of unmetastatic cervical squamous cell carcinoma, and 19 cases of metastatic cervical squamous cell carcinoma. RNA interference technique was used to knock down YB-1, E6, and Snail genes. Quantitative polymerase chain reaction, western blot, and transwell experiment were used to detect RNA, protein, and cell invasion of cervical cancer cell lines Hela and C33A, respectively. RESULTS: First, YB-1 knockdown significantly reduced messenger RNA (mRNA) and protein levels of Snail, followed by the increased mRNA and protein levels of E-cad and the decreased invasive ability in both Hela (human papillomavirus [HPV] 18+) and C33A (HPV-) cell lines. Second, YB-1 and Snail protein were correlatively expressed in the group order of metastatic cervical squamous cell carcinoma > unmetastatic cervical squamous cell carcinoma > CINs > cervicitis, with the inverse expression mode of E-cad in the group order, P value less than 0.01, between any 2 groups. Finally, HPV18 E6 knockdown reduced the mRNA and protein levels of YB-1 and Snail in Hela cells. CONCLUSIONS: The results firstly reported that YB-1 whose mRNA expression is regulated by HPV18 E6 promotes epithelial-mesenchymal transition and progression of cervical cancer via enhancing the expressions of Snail, which indicated that YB-1/Snail/epithelial-mesenchymal transition axis could have a potential use in the diagnosis and therapy of cervical cancer metastasis as a cancer marker and molecular target.

HPV18 E7 induces the over-transcription of eIF4E gene in cervical cancer.

OBJECTIVES: Eukaryotic translation initiation factor 4E (eIF4E) is overexpressed in cervical cancer (CC). However, the molecular mechanisms are unclear. This study aimed to investigate the molecular mechanism of eIF4E gene overexpression in CC. MATERIALS AND METHODS: The human papillomavirus (HPV) type 18 E7 and eIF4E mRNAs were measured following knock down or overexpression of E7 gene by RT-PCR and real-time PCR. Cell counting kit-8 assay was used to determine the cell proliferation. Flow cytometry was used to analyze the cell cycle and apoptosis. Transwell system was employed to determine the cell migration. RESULTS: Overexpression of E7 gene increased eIF4E mRNA level by 24.3% (P<0.01) in HPV negative C33A cells. Knock down of E7 decreased markedly eIF4E mRNA by 73% (P<0.01) in HPV18 positive HeLa cells. Under the state of high expression of E7, 1) up-regulation of eIF4E drastically promoted the cell proliferation, cell cycle and cell migration, and inhibited the cell apoptosis. 2) down-regulation of eIF4E significantly inhibited the cell proliferation, cell cycle and the ability of cell migration, and also promoted the apoptosis of cervical cancer cells. CONCLUSION: HPV E7 induced eIF4E gene over transcription which might be a new marker for CC. The finding broadens the understanding of the CC carcinogenesis.

Interleukin 37 Expression Inhibits STAT3 to Suppress the Proliferation and Invasion of Human Cervical Cancer Cells.

OBJECTIVES: The most recently discovered cytokine interleukin 37 (IL-37) received growing attention. Its function on tumor is largely unknown. Here, we investigated the biological function of IL-37 on cervical cancer (CC). Materials and methods : HPV(+) Hela cells and HPV(-) C33A cells were used. RT-qPCR was performed to detect the transcription of IL-37, STAT3, TNF-αand IL-1ß. Western blotting was used for protein detection. CCK-8 assay and transwell assay were employed for cell proliferation and invasion detection, respectively. Results : Successful gene transfection of IL-37 suppressed the proliferation and invasion of CC. Interestingly, IL-37 showed higher anticancer ability in HPV(+) Hela cells than that in HPV(-) C33A cells. Then, the molecular mechanism of IL-37 anticancer was explored. Firstly, we found that IL-37 inhibited STAT3 expression at both mRNA and protein levels. IL-37 also down regulated the phosphorylation of STAT3. Secondly, blockage of STAT3 using siRNAs reduced significantly the ability of IL-37 to suppress cell proliferation and invasion. Thirdly, STAT3 knockdown reduced markedly the inhibition of IL-37 on the transcription of tumor-derived TNF-α and IL-1ß, indicating the contribution of STAT3 for the cancer associated antiinflammation of IL-37. Finally, STAT3 up regulation restored the ability of cell proliferation, cell invasion and the expression of inflammatory cytokines, TNF-α and IL-1ß. Conclusions : IL-37 suppressed cell proliferation and invasion of CC and STAT3 is involved in this process. Thus, IL-37 emerges as a new anticancer cytokine for CC. This study demonstrated a new biological function of IL-37 and offered a potential molecule for CC treatment.

Dehydrocostus Lactone Inhibits Proliferation, Antiapoptosis, and Invasion of Cervical Cancer Cells Through PI3K/Akt Signaling Pathway.

OBJECTIVES: Recent studies found that dehydrocostus lactone (DHC), a traditional Chinese medicine in curing chronic ulcer and inflammation, can inhibit several type of tumor cells. The purpose of this study was to define the role of DHC on cervical cancer cells and to explore its mechanism of action. METHODS: We used DHC alone or in combination with PI3K/Akt-specific inhibitor LY294002 (LY) to treat Hela cells [human papillomavirus (HPV)-18 positive] and C33a cells (HPV negative). The proliferation, apoptosis, and Akt activation were assessed. Cell invasive ability was assayed in transwell chambers. RESULTS: We found that DHC significantly inhibited proliferation, antiapoptosis, and invasion of both cells, and reduced the level of p-Akt phosphorylation in these cells, in a dose- or time-dependent manner. In addition, these inhibitions of DHC were significantly strengthened by LY. CONCLUSIONS: The result suggested that DHC plays a potent role in anticervical cancer in multiple biological aspects through PI3K/Akt signaling pathway, independently of HPV infection. This finding surely adds new knowledge to understand the role of DHC in fighting cancers.

Dehydrocostus lactone suppressed the proliferation, migration, and invasion of colorectal carcinoma through the downregulation of eIF4E expression.

Dehydrocostus lactone (DHC) is the main active ingredient extracted from a traditional Chinese medicine called Radix Aucklandiael. A few studies recently showed that DHC has anticancer potential. However, no reports exist as yet on the effects of DHC on colorectal carcinoma (CRC). This study aimed to determine whether and how DHC functions in CRC cells. After treatment with DHC, both Lovo and SW480 cells were significantly inhibited in their proliferation, cell cycle progression, migration, and invasion abilities in a dose-dependent and/or treatment time-dependent manner. Also, DHC significantly increased the apoptosis rate of SW480 cells, but not Lovo cells. The expression of eukaryotic translation initiation factor 4E (eIF4E), which was originally highly expressed in both cells, was significantly decreased by DHC. The inhibition of proliferation, migration, and invasion was significantly attenuated by the ectopic transfection of eIF4E, and was promoted by the knockdown of eIF4E in Lovo cells. To the best of our knowledge, this is the first time it has been shown that DHC suppressed the proliferation, cell cycle progression, antiapoptosis, and migration and invasion capabilities of CRC cells by the downregulation of eIF4E expression. In terms of the overexpression of eIF4E in many cancers, it was speculated that DHC might also play an anticancerous role by suppressing eIF4E expression. This discovery could lay the foundations for advancing our understanding of the anticancerous mechanism of DHC and developing DHC into a novel and effective natural anticancer therapeutic.

Pokemon enhances proliferation, cell cycle progression and anti-apoptosis activity of colorectal cancer independently of p14ARF-MDM2-p53 pathway.

Pokemon has been showed to directly suppress p14(ARF) expression and also to overexpress in multiple cancers. However, p14(ARF)-MDM2-p53 pathway is usually aberrant in colorectal cancer (CRC). The aim is to confirm whether Pokemon plays a role in CRC and explore whether Pokemon works through p14(ARF)-MDM2-p53 pathway in CRC. Immunohistochemistry for Pokemon, p14(ARF) and Mtp53 protein was applied to 45 colorectal epitheliums (CREs), 42 colorectal adenomas (CRAs) and 66 CRCs. Pokemon was knocked down with RNAi technique in CRC cell line Lovo to detect mRNA expression of p14(ARF) with qRT-PCR, cell proliferation with CCK8 assay, and cell cycle and apoptosis with flowcytometry analysis. The protein expression rates were significantly higher in CRC (75.8%) than in CRE (22.2 %) or CRA (38.1%) for Pokemon and higher in CRC (53.0%) than in CRE (0) or CRA (4.8%) for Mtp53, but not significantly different in CRC (86.4 %) versus CRE (93.3%) or CRA (90.5 %) for p14(ARF). Higher expression rate of Pokemon was associated with lymph node metastasis and higher Duke's stage. After knockdown of Pokemon in Lovo cells, the mRNA level of p14(ARF) was not significantly changed, the cell proliferation ability was decreased by 20.6%, cell cycle was arrested by 55.7% in G0/G1 phase, and apoptosis rate was increased by 19.0%. Pokemon enhanced the oncogenesis of CRC by promoting proliferation, cell cycle progression and anti-apoptosis activity of CRC cells independently of p14(ARF)-MDM2-p53 pathway. This finding provided a novel idea for understanding and further studying the molecular mechanism of Pokemon on carcinogenesis of CRC.

LMP1 stimulates the transcription of eIF4E to promote the proliferation, migration and invasion of human nasopharyngeal carcinoma.

Eukaryotic translation initiation factor 4E (eIF4E) is the rate-limiting translation initiation factor for many oncogenes. Previous studies have shown eIF4E overexpression in nasopharyngeal carcinoma (NPC). We aimed to study whether viral oncogene latent membrane protein 1 (LMP1) stimulates the transcription of eIF4E to promote NPC malignancy. In NPC cell lines (CNE1 and CNE2), ectopic LMP1 significantly increased the mRNA and protein levels of eIF4E and the transcriptional activity of the eIF4E promoter in a LMP1-plasmid-transfected dose-dependent manner. As a backward experiment, knocking down of LMP1 significantly reduced eIF4E mRNA in B95-8 cells. In the high LMP1 expression condition, knocking down of c-Myc significantly reduced eIF4E mRNA in both NPC and B95-8 cells, and knocking down of eIF4E significantly inhibited the tumor proliferation, migration and invasion promoted by LMP1. The results indicated that LMP1 stimulates the transcription of eIF4E via c-Myc to promote NPC. To the best of our knowledge, this is the first evidence that LMP1 stimulates the transcription of eIF4E. This might be an important cause of the overexpression of eIF4E in NPC and be the novel mechanism by which LMP1 initiates cancer. LMP1-stimulated eIF4E initiates the translation of those oncogenes transcriptionally activated by LMP1 to amplify and pass down the carcinogenesis signals launched by LMP1.

Annexin A3 is associated with a poor prognosis in breast cancer and participates in the modulation of apoptosis in vitro by affecting the Bcl-2/Bax balance.

OBJECTIVE: Annexins are a family of intracellular proteins that bind membrane phospholipids in a Ca(2+) concentration-dependent manner. Several annexins play important roles during tumor progression. However, little is known about the clinical implications and biological functions of Annexin A3 in breast cancer. METHODS: Using immunohistochemistry, we analyzed 60 breast cancers for the levels of annexin A3 and investigated the correlation of its expression change with patient's survival via Kaplan-Meier survival analysis. Furthermore, via knockdown of Annexin A3 expression in breast cancer cells with special siRNA, the role of Annexin A3 in the proliferation and apoptosis of breast cancer cells was examined. RESULTS: Annexin A3 was expressed at higher level in breast cancer than that in normal breast tissue. The expression of Annexin A3 in human breast carcinoma closely correlated with tumor size and axillary lymph node metastasis. Kaplan-Meier survival analysis revealed a significant inverse correlation between strong Annexin A3 expression and overall patient survival. Moreover, Annexin A3 overexpression was inversely associated with Bax staining and the apoptosis index. Annexin A3 small interfering RNA in MCF-7 and MDA-MB-435 could inhibit cell proliferation, decrease Bcl-2 mRNA and protein expression, and increase Bax mRNA and protein expression. CONCLUSION: Our findings indicated that Annexin A3 might be a novel and potential prognostic marker for patients with breast cancer and be involved in regulating apoptosis by affecting Bcl-2/Bax balance.

HPV E6 induces eIF4E transcription to promote the proliferation and migration of cervical cancer.

Increasing evidence has placed eukaryotic translation initiation factor 4E (eIF4E) at the hub of tumor development and progression. Several studies have reported that eIF4E is over-expressed in cervical cancer; however, the mechanism remains elusive. The results of this study further confirm over-expression of eIF4E in cervical cancer tumors and cell lines, and we have discovered that the transcription of eIF4E is induced by protein E6 of the human papillomavirus (HPV). Moreover, regulation of eIF4E by E6 significantly influences cell proliferation, the cell cycle, migration, and apoptosis. Therefore, eIF4E emerges as a key player in tumor development and progression and a potential target for CC treatment and prevention.

EIF4E over-expresses and enhances cell proliferation and cell cycle progression in nasopharyngeal carcinoma.

Eukaryotic translation initiation factor 4E (eIF4E) is involved in integration and amplification of many carcinogenesis signals in tumors. However, it remains unclear whether eIF4E over-expresses in NPC and whether it is associated with the development of NPC. Here, we analyzed the expression state of eIF4E, c-Myc, and MMP9 in 24 nasopharyngitises and 64 nasopharyngeal carcinomas (NPC) tissues and studied the influences of eIF4E on the proliferation and cell cycle in NPC cell lines. The results indicate that eIF4E might over-express in NPC and the over-expression of eIF4E promotes NPC growth and cell cycle progression through enhancing the translational expression of c-Myc and MMP9. The finding certainly adds new knowledge in the understanding of the carcinogenesis of NPC and provides a potential molecular target for the NPC therapy and prevention.

Heparanase overexpression participates in tumor growth of cervical cancer in vitro and in vivo.

Expression of heparanase is associated with invasion, metastasis and angiogenesis of a variety of human cancers. However, the roles of heparanase in cervical cancer are not clear. The aim of this study is to determine whether up-regulation of heparanase expression can promote growth of cervical cancer in vitro and in vivo. Heparanase protein expression was analyzed in cervical cancer patients using immunohistochemistry. In addition, expression of heparanase was also examined in cervical cancer cell lines. A series of in vivo and in vitro assays was performed to elucidate the role of heparanase in tumor growth of cervical cancer. Positive rate of heparanase was 63.3 % (38/60) in cervical cancer patients by immunohistochemistry, and it was significantly correlated with tumor size and clinical stage (P < 0.05). Overexpression of heparanase inhibited apoptosis of cervical cancer cells. Moreover, ectopic overexpression of heparanase in cervical cancer cells promoted proliferation of cervical cancer cells in vitro and tumor growth in vivo. These results suggest that heparanase participates in tumor growth of cervical cancer by influencing the proliferation and apoptosis of cervical cancer cells, and heparanase could be used as an effective therapeutic target for cervical cancer.

Up-regulation of Foxp3 participates in progression of cervical cancer.

Foxp3 was identified as a key protein in mediating inhibitory functions of regulatory T cell (Treg). Foxp3 was thought to express only in the T cell lineage until recently when some researches reported that Foxp3 was also expressed by cancer cells. In this study, we describe for the first time the expression of Foxp3 in cervical cancer. Progression from cervical intraepithelial neoplasia (CIN) to cervical cancer is a multistep process initiated by persistent infection with high-risk human papillomavirus (HPV). P16(INK4a) is a crucial marker of HPV integration into host cells. In the present study, expressions of Foxp3 and P16(INK4a) in CIN and cervical cancer were detected by immunohistochemistry. Our results found expression level of Foxp3 was increased during the progression of cervical neoplasia. Moreover, up-regulation of Foxp3 appeared to be correlated with the expression of P16(INK4a). Examination of the role of Foxp3 in differentiation by double immunostaining for cytokeratin 10 (CK10) showed significant association between Foxp3 expression and differentiation (Foxp3 vs CK10). Furthermore, positive expression of Foxp3 was correlated with tumor size. These data suggest that Foxp3 may play an important role in differentiation and growth of cervical cancer cells. Our findings provide new insights regarding the role of Foxp3 in differentiation and its association with HPV infection during the development of cervical cancer.

A global view of the oncogenic landscape in nasopharyngeal carcinoma: an integrated analysis at the genetic and expression levels.

Previous studies have reported that the tumour cells of nasopharyngeal carcinoma (NPC) exhibit recurrent chromosome abnormalities. These genetic changes are broadly assumed to lead to changes in gene expression which are important for the pathogenesis of this tumour. However, this assumption has yet to be formally tested at a global level. Therefore a genome wide analysis of chromosome copy number and gene expression was performed in tumour cells micro-dissected from the same NPC biopsies. Cellular tumour suppressor and tumour-promoting genes (TSG, TPG) and Epstein-Barr Virus (EBV)-encoded oncogenes were examined. The EBV-encoded genome maintenance protein EBNA1, along with the putative oncogenes LMP1, LMP2 and BARF1 were expressed in the majority of NPCs that were analysed. Significant downregulation of expression in an average of 76 cellular TSGs per tumour was found, whilst a per-tumour average of 88 significantly upregulated, TPGs occurred. The expression of around 60% of putative TPGs and TSGs was both up-and down-regulated in different types of cancer, suggesting that the simplistic classification of genes as TSGs or TPGs may not be entirely appropriate and that the concept of context-dependent onco-suppressors may be more extensive than previously recognised. No significant enrichment of TPGs within regions of frequent genomic gain was seen but TSGs were significantly enriched within regions of frequent genomic loss. It is suggested that loss of the FHIT gene may be a driver of NPC tumourigenesis. Notwithstanding the association of TSGs with regions of genomic loss, on a gene by gene basis and excepting homozygous deletions and high-level amplification, there is very little correlation between chromosomal copy number aberrations and expression levels of TSGs and TPGs in NPC.

Expression of 14-3-3γ in patients with breast cancer: correlation with clinicopathological features and prognosis.

AIM: Protein 14-3-3γ is an important member of the 14-3-3 family that play important roles in the regulation of various cellular processes. The aim of the study is to investigate the association between 14-3-3γ expression and the clinicopathological features of patients with breast cancer. METHODS: The expression of 14-3-3γ was detected by Western blot in both foci of breast cancer and adjacent non-cancerous tissues. In addition, 14-3-3γ expression was analyzed by immunohistochemistry in 60 clinicopathologically characterized breast cancer cases. The association of 14-3-3γ expression with survival of the patients were analyzed. RESULTS: The expression level of 14-3-3γ protein in breast cancer were significantly higher than that in non-cancerous mammary gland tissues. Moreover, high expression of 14-3-3γ correlated with tumor size and tumor grade (all P<0.05). Patients with high 14-3-3γ expression had worse overall survival rate than that with low expression (P < 0.05). Furthermore, multivariate analysis showed that 14-3-3γ expression was an independent predictor of overall survival (HR, 0.196; 95%CI, 0.043-0.892; P = 0.035). CONCLUSIONS: Our data suggest for the first time that the increased expression of 14-3-3γ in breast cancer is associated significantly with tumor progression and poor prognosis. 14-3-3γ may be a novel and potential prognostic marker for breast cancer.