LINC02561 promotes metastasis in HCC via HIF1-α/NDRG1/UPF1 axis.

In the entire world, hepatocellular carcinoma (HCC) is one of the most frequent cancers that lead to death. Experiments on the function of long non-coding RNAs in the emergence of malignancies, including HCC, are ongoing. As a crucial RNA monitoring mechanism in eucaryotic cells, nonsense-mediated mRNA decay (NMD) can recognize and destroy mRNAs, which has an premature termination codons (PTC) in the open reading frame to prevent harmful buildup of truncated protein products in the cells. Nonsense transcript regulator 1 (Up-frameshift suppressor 1, UPF1), as a highly conserved RNA helicase and ATPase, plays a key role in NMD. Our laboratory screened out the highly expressed lncRNA LINC02561 in HCC from the TCGA database. Further research found that LINC02561 enhanced the invasion and transition abilities of liver cancer cells by regulating the protein N-Myc downstream regulated 1 (NDRG1). Hypoxia inducible factor-1 (HIF-1α) can bonded to LINC02561 promoters under hypoxic conditions, thereby promoting the upregulation of LINC02561 expression in liver cancer cells. LINC02561 competes with NDRG1 mRNA to bind UPF1, thereby preventing the degradation of NDRG1 mRNA to facilitate NDRG1 protein level. Taken together, the HIF1α-LINC02561-UPF1-NDRG1 regulatory axis could be an entirely novel target of liver cancer-related treatment.

Overexpression of CENPF is associated with progression and poor prognosis of lung adenocarcinoma.

Background and aim: The molecular signatures of lung adenocarcinoma (LUAD) are not well understood. Centromere protein F (CENPF) has been shown to promote oncogenesis in many cancers; however, its role in LUAD has not been illustrated. We explored the role of CENPF in LUAD. Methods: CENPF expression level was investigated in public online database firstly, the prognosis of CENPF in LUAD were also assessed by Kaplan-Meier analysis. Then quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed using 13 matched pairs of clinical LUAD tissue samples. Subsequently, the impact of CENPF expression on cell proliferation, cell cycle, apoptosis, colony formation was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), flow cytometric analysis and colony formation assay, respectively. Finally, experimental xenograft lung cancer model of nude mice armpit of right forelimb to determine the effect of CENPF on LUAD tumorigenesis. Results: CENPF mRNA expression was significantly elevated in LUAD tissues compared with adjacent non-tumor lung tissues in Gene Expression Profiling Interactive Analysis (GEPIA) (P < 0.001). Up-regulated CENPF was remarkably positively associated with pathological stage, relapse free survival (RFS) as well as overall survival (OS) of LUAD patients. Besides, CENPF knockdown greatly suppressed A549 cell proliferation, induced S phase arrest, promoted apoptosis and decreased colony numbers of LUAD cells. Furthermore, knockdown of CENPF significantly inhibited the tumor growth of the LUAD cells in an experimental xenograft lung cancer model of nude mice armpit of right forelimb. Conclusion: Taken together, these results demonstrated that CENPF may serve as a potential biomarker of prognostic relevance and a potential therapeutic target for LUAD.

The role of mTOR in ovarian Neoplasms, polycystic ovary syndrome, and ovarian aging.

The mammalian target of rapamycin, mTOR, is a serine-threonine protein kinase downstream of the phosphatidylinositol 3-kinase (PI3K)-AKT axis. The pathway can regulate cell growth, proliferation, and survival by activating ribosomal kinases. Recent studies have implicated the mTOR signaling pathway in ovarian neoplasms, polycystic ovary syndrome (PCOS) and premature ovarian failure (POF). Preclinical investigations have demonstrated that the PI3K/AKT/mTOR pathway is frequently activated in the control of various ovarian functions. mTOR allows cancer cells to escape the normal biochemical system and regulates the balance between apoptosis and survival. Some recent studies have suggested that involvement of the mTOR signaling system is an important pathophysiological basis of PCOS. Overexpression of the mTOR pathway can impair the interaction of cumulus cells, lead to insulin resistance, and affect the growth of follicles directly. The roles of mTOR signaling in follicular development have been extensively studied in recent years; abnormalities in this process lead to a series of pathologies such as POF and infertility. To improve understanding of the role of the mTOR signaling pathway in the pathogenesis and development of ovarian diseases, here we review the roles of mTOR signaling in such diseases and discuss the corresponding therapeutic strategies that target this pathway. Clin. Anat. 31:891-898, 2018. © 2018 Wiley Periodicals, Inc.

Downregulation of selenium-binding protein 1 is associated with poor prognosis in lung squamous cell carcinoma.

BACKGROUND: We found that selenium-binding protein 1 (SBP1) was progressively decreased in the human bronchial epithelial carcinogenic processes. Knockdown of SBP1 in immortalized human bronchial epithelial cell line 16HBE cells significantly increased the efficiency of B[a]P-induced cell transformation. However, the relationship between SBP1 expression and clinicopathological factors of patients has not been defined completely. The specific role of SBP1 in prognosis of lung squamous cell carcinoma (LSCC) is still unknown. METHODS: Tissue samples from 82 patients treated by pulmonary lobectomy for LSCC were used. Immunohistochemistry and western blotting were used to detect the expressions of SBP1 protein. The relationships between the expression level of SBP1 and the clinicopathological features of patients were analyzed. Cox proportional hazard regression analysis and Kaplan-Meier method were used to perform survival analysis. RESULTS: Expressions of SBP1 proteins were significantly lower in LSCC tissues than that in the corresponding normal bronchial epithelium (NBE) tissues (P = 0.000). In LSCC, The expression levels of SBP1 had not correlated with patients' age, gender, smoking state, primary tumor stages (T), TNM clinical stages, and distant metastasis (M) (P > 0.05). However, downregulation of SBP1 was significantly associated with higher lymph node metastasis and lower overall survival rate (P < 0.05). Cox regression analysis indicated low expressions of SBP1 can be an independent prognostic factor for poor overall survival in LSCC patients (P = 0.002). CONCLUSIONS: Downregulation of SBP1 may play a key role in the tumorigenic process of LSCC. SBP1 may be a novel potential prognostic factor of LSCC.

Annexin A1: a new biomarker for predicting nasopharyngeal carcinoma response to radiotherapy.

Radiotherapy is the primary treatment for nasopharyngeal carcinoma (NPC), but radioresistance remains a serious obstacle to successful treatment in many cases. Therefore, the biomarkers for predicting NPC response to radiotherapy are very important for targeted therapy and individualized radiotherapy of NPC. Accumulating evidences have shown that Annexin A1 was correlated with NPC radioresistance. First, Annexin A1 is a potential tumor suppressor gene, and can regulate tumor cell proliferation and apoptosis, thus abnormal expression of Annexin A1 in NPC affects apoptosis of tumor cells induced by ionizing radiation and radiotherapeutic efficacy. Second, Annexin A1 is one of the proteins that are involved in p53-mediated radioresponse in NPC, and it might be related to NPC radioresistance. Third, the expression level of Annexin A1 is down-regulated in NPC, and is correlated with metastasis, recurrence and poor prognosis of NPC, thus Annexin A1 downregulation may increase NPC radioresistance, leading to poor prognosis. Last but not the least, Annexin A1 is closely related with tumor chemoresistance, whereas radioresistance is similar to chemoresistance in many aspects, thus Annexin A1 may also be involved in NPC radioresistance. Based on the above mentions, we hypothesize that Annexin A1 is closely correlated with NPC radioresistance and is an important new biomarker for predicting NPC response to radiotherapy.

Prognostic value of Wnt inhibitory factor-1 expression in hepatocellular carcinoma that is independent of gene methylation.

Recently, Wnt inhibitory factor-1 (WIF-1) was found to be epigenetically inactivated in several solid tumors, but the biological and clinical relevance of WIF-1 methylation and expression status in hepatocellular carcinoma (HCC) are still unclear. In the present study, reverse transcription polymerase chain reaction (PCR) and methylation-specific PCR were used to examine the WIF-1 expression and methylation in HCC cell lines. In addition, methylation and expression status of WIF-1 in 105 HCC cases were correlated with clinicopathological parameters and prognosis after tumor resection. WIF-1 was expressed in one HCC cell line and L02, both of which were not methylated in promoter region. DNA hypermethylation of WIF-1 promoter was identified in the other four HCC cell lines without WIF-1 expression. In neoplastic and non-neoplastic tissue samples, the rates of WIF-1 methylation were 61.9% and 37.1% (P = 0.001), respectively. WIF-1 was significantly downregulated in neoplastic tissues at messenger ribonucleic acid (mRNA) level, as compared to adjacent non-neoplastic tissues (P = 0.006). A significant inverse association was observed between WIF-1 methylation of and WIF-1 expression (P 0.017, R = -0.232). Methylation of WIF-1 was not associated with patient survival. In contrast, patients whose tumors exhibited negative WIF-1 mRNA expression had lower rates of overall survival. These findings suggested that aberrant methylation of WIF-1 is a common event in hepatocarcinogenesis. In addition, expression, but not methylation, of WIF-1 is a predictor of good outcome in patients undergoing resection of HCC.

Proteomic analysis of the stroma-related proteins in nasopharyngeal carcinoma and normal nasopharyngeal epithelial tissues.

The stroma surrounding cancer cell population is increasingly recognized as playing an important role in cancer proliferation, invasion, and metastasis. To identify the stromal proteins involved in nasopharyngeal carcinoma (NPC) carcinogenesis, differences in protein expression of the stroma from NPC and normal nasopharyngeal epithelium tissues (NNET) were assessed using a comparative proteomic approach combined with laser capture microdissection (LCM). LCM was performed to purify stromal cells from NPC and NNET, respectively. Proteins between the pooled microdissected tumor and normal stroma were separated by two-dimensional electrophoresis (2-DE) and differential proteins were identified by mass spectrometry (MS). Sixty differential proteins between normal stroma (NS) and tumor stroma (TS) were identified, and the expression of CapG protein was further confirmed by western blotting and immunohistochemical analysis. Our results will be helpful to study the role of stroma in the NPC carcinogenesis and may provide helpful clues for pathogenesis, early diagnosis, and progression of NPC.

Quantitative proteomic analysis of differential proteins in the stroma of nasopharyngeal carcinoma and normal nasopharyngeal epithelial tissue.

The importance of stromal cells and the factors that they expressed during cancer initiation and progression have been highlighted by recent literature. To identify the stromal proteins involved in nasopharyngeal carcinoma (NPC) carcinogenesis, we assessed differences in protein expression of the stroma from NPC and normal nasopharyngeal epithelium tissues (NNET) using a quantitative proteomic approach combined with laser capture microdissection (LCM). LCM was performed to purify stromal cells from the NPC and NNET, respectively. The differential proteins between the pooled microdissected tumor and normal stroma were analyzed by two-dimensional difference gel electrophoresis (2D-DIGE) combined with mass spectrometry (MS). Twenty differential proteins were identified, and the expression and location of two differential proteins (L-plastin and S100A9) were further confirmed by Western blotting and immunohistochemical analysis. Our results will be helpful to study the role of stroma in the NPC carcinogenesis, as well as discover the interaction between NPC cells and their surrounding microenvironment.

[Expression and methylation of adenomatous polyposis coli gene in endometrioid adenocarcinoma].

BACKGROUND & OBJECTIVE: Endometrial carcinoma is a common malignant tumor of female reproductive system, with an increasing incidence in China. Adenomatous polyposis coli (APC) gene, a tumor suppressor gene, is expressed in many tissues, and has a certain relationship with ovarian cancer. This study was to observe the expression and DNA methylation of APC gene in endometrioid adenocarcinoma, and explore its correlations to the occurrence and development of this disease. METHODS: The methylation, mRNA and protein expression of APC gene were detected by methylation-specific polymerase chain reaction (PCR), reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry in 30 specimens of normal proliferative endometrium, 30 specimens of atypical hyperplastic endometrium and 60 specimens of endometrioid adenocarcinoma. RESULTS: The methylation rate of APC gene was significantly higher, the positive rates of APC mRNA and protein were significantly lower in endometrioid adenocarcinoma than in atypical hyperplastic endometrium and normal proliferative endometrium (65.0% vs. 33.3% and 23.3%, 33.3% vs. 63.3% and 73.3%, 30.0% vs. 50.0% and 66.7%,P<0.05). There was no significant difference between atypical hyperplastic endometrium and normal endometrium (P>0.05). APC methylation was positively correlated to APC mRNA expression. CONCLUSION: The expression and DNA methylation of APC gene are certainly related with the occurrence and development of endometrioid adenocarcinoma.