[Influence of Pre-treatment Lymphocyte/Monocyte Ratio and Neutrophil/Lymphocyte Ratio on the Prognosis of Patients with Extranodal NK/T-Cell Lymphoma].

OBJECTIVE: To explore the influence of lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio (NLR) on the prognosis of patients with extranodal NK/T cell lymphoma (ENKTL). METHODS: The clinical data of 203 patients with ENKTL admitted to the First Affiliated Hospital of Zhengzhou University from January 2011 to January 2020 were retrospectively analyzed. The ROC curve determined the limit values of LMR and NLR; Categorical variables were compared using a chi-square test, expressed as frequency and percentage (n,%). Continuous variables were expressed as medians and extremes and compared with the Mann-Whitney U test; Progression-free survival (PFS) and overall survival (OS) of different grouped LMR and NLR patients were analyzed using Kaplan-Meier curves and compared with log-rank tests. The COX proportional risk regression model was used to perform one-factor and multi-factor analysis of PFS and OS. RESULTS: The optimal critical values of LMR and NLR were determined by the ROC curve, which were 2.60 and 3.40, respectively. LMR≤2.60 was more likely to occur in patients with bone marrow invasion (P=0.029) and higher LDH (P=0.036), while NLR≥3.40 was more likely to occur in patients with higher ECOG scores (P=0.002), higher LDH (P=0.008), higher blood glucose (P=0.024), and lower PLT (P=0.010). Kaplan-Meier survival analysis showed that PFS and OS of patients in the high LMR group were significantly better than the low LMR group, while PFS and OS in the low NLR group were significantly better than the high NLR group. The results of multivariate COX analysis showed that EBV-DNA positive (P=0.047), LMR≤2.60 (P=0.014), NLR≥3.40 (P=0.023) were independent risk factors affecting PFS in patients with ENKTL. LMR≤2.60 (P<0.001), NLR≥3.40 (P=0.048), and high ß2-MG (P=0.013) were independent risk factors affecting OS in patients with ENKTL. CONCLUSION: Low LMR and high NLR before treatment are associated with poor prognosis in patients with ENKTL, which also can be used as an easily testable, inexpensive, and practical prognostic indicator in the clinic.

Long non-coding RNA ZNF667-AS1 retards the development of esophageal squamous cell carcinoma via modulation of microRNA-1290-mediated PRUNE2.

Abnormal long non-coding RNAs (lncRNAs) have been detected in esophageal squamous cell carcinoma (ESCC). Here, we focused on lncRNA ZNF667-AS1 and its downstream mechanism in ESCC progression. Differentially expressed lncRNAs in ESCC were predicted by bioinformatics analysis. ZNF667-AS1, microRNA-1290 (miR-1290), and prune homolog 2 with BCH domain (PRUNE2) expression was determined with their relationship in cell biological processes analyzed also by means of gain- and loss-of-function assays. Xenograft mouse models were performed to re-produce the in vitro findings. We found a decline in ZNF667-AS1 expression in ESCC tissues and cell lines. ZNF667-AS1 overexpression indicated a favorable prognosis of ESCC sufferers. ZNF667-AS1 overexpression suppressed ESCC cell malignant potentials. ZNF667-AS1 reduced miR-1290 to result in upregulation of the miR-1290 target gene PRUNE2. The inhibiting property of ZNF667-AS1 on the malignant characteristics of ESCC cells was achieved by disrupting the miR-1290-mediated downregulation of PRUNE2. ZNF667-AS1 suppressed the tumorigenesis of ESCC in vivo. Collectively, our study demonstrates that ZNF667-AS1 can function as a tumor suppressor in ESCC by upregulating PRUNE2 and downregulating miR-1290.

Porf-2 Inhibits Tumor Cell Migration Through the MMP-2/9 Signaling Pathway in Neuroblastoma and Glioma.

Tumor migration and invasion are key pathological processes that contribute to cell metastasis as well as treatment failure in patients with malignant tumors. However, the mechanisms governing tumor cell migration remain poorly understood. By analyzing the tumor-related database and tumor cell lines, we found that preoptic regulatory factor-2 (Porf-2) is downexpressed in both neuroblastoma and glioma. Using in vitro assays, our data demonstrated that the expression of Porf-2 inhibits tumor cell migration both in neuroblastoma and glioma cell lines. Domain-mutated Porf-2 plasmids were then constructed, and it was found that the GAP domain, which plays a role in the inactivation of Rac1, is the functional domain for inhibiting tumor cell migration. Furthermore, by screening potential downstream effectors, we found that Porf-2 can reduce MMP-2 and MMP-9 expression. Overexpression of MMP-2 blocked the inhibitory effect of Porf-2 in tumor cell migration both in vitro and in vivo. Taken together, we show for the first time that Porf-2 is capable of suppressing tumor cell migration via its GAP domain and the downregulation of MMP-2/9, suggesting that targeting Porf-2 could be a promising therapeutic strategy for nervous system tumors.

MicroRNA-155 acts as a diagnostic and prognostic biomarker for oesophageal squamous cell carcinoma.

MicroRNA-155 is over-expressed in many human cancers, but researches on its association with malignant oesophageal squamous cell carcinoma (ESCC) are limited. The aim of the present study was to evaluate the potential value of miR-155 as a biomarker for ESCC diagnosis and prognosis. In this study, we found that miR-155 was significantly increased in ESCC tissues compared with the paired adjacent tissues and healthy normal controls (p < .001), according to qRT-PCR, which suggested that miR-155 might act as an oncogene in ESCC. In addition, clinical features such as the depth of tumour invasion, tumour size, and TNM stage were all proved to impact the expression of miR-155 (p < .01). Then, ROC curve analysis, reaching an AUC of 0.870, and a sensitivity and specificity of 83.5% and 77.5%, respectively, revealed that miR-155 was a predictive factor for ESCC. As well, high expression of miR-155 was associated with poor overall survival of the patients (log-rank test, p = .004), according to Kaplan-Meier analysis. MiR-155 might be an independent predictor for overall survival in ESCC patients, manifested by Cox regression analysis (HR = 16.94, 95%CI = 3.33-86.12, p = .001). Taken together, miR-155 could be an independent diagnostic and prognostic biomarker for ESCC.

Silencing lncRNA LOC101928963 Inhibits Proliferation and Promotes Apoptosis in Spinal Cord Glioma Cells by Binding to PMAIP1.

Long non-coding RNAs (lncRNAs) have been widely highlighted due to their involvement in various types of cancers, including glioma; however, the exact mechanism and function by which they operate in regard to spinal cord glioma remain poorly understood. LOC101928963 was screened out for its differential expression in spinal cord glioma by microarray analysis. Therefore, this study was conducted to investigate the modulatory effects of LOC101928963 on spinal cord glioma by binding to phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1). The expression of LOC101928963 and LOC101928963 was characterized in spinal cord glioma tissues, and their interaction was examined by dual-luciferase reporter gene assay. Cells with LOC101928963 that exhibited elevated or suppressed levels of PMAIP1 were established to substantiate the mechanism between LOC101928963 and PMAIP1. qRT-PCR and western blot methods were subsequently applied to determine the expression of cell-proliferation- and apoptosis-related genes in response to the alterations of LOC101928963 and PMAIP1. Glioma cell proliferation and apoptosis were assessed by MTT assay and flow cytometry. Decreased cell apoptosis and PMAIP1 expression, as well as overexpressed LOC101928963, were exhibited among spinal cord glioma tissues. LOC101928963 overexpression was observed to promote cell proliferation and cell-cycle entry and inhibit the process of apoptosis. PMAIP1, a target of LOC101928963, displayed a downregulated level following the elevation of LOC101928963. The present results strongly emphasize the neutralization effect of PMAIP1 overexpression on spinal cord glioma progression induced by the overexpression of LOC101928963. The data obtained during the study highlighted the inhibitory role of LOC101928963 silencing in spinal cord glioma through the increase in PMAIP1, which suggests a potential target in the treatment of spinal cord glioma.

Long noncoding RNA SMAD5-AS1 acts as a microRNA-106a-5p sponge to promote epithelial mesenchymal transition in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignant epithelial cancer of the head and neck with high prevalence in southern China, which is accompanied by notable invasiveness and metastasis. Long noncoding RNAs (lncRNAs) participate in the progression of various cancers including NPC. Microarray-based analysis identified highly expressed lncRNA mothers against decapentaplegic homolog 5 (SMAD5)-antisense RNA 1 (AS1) related to NPC. Interestingly, it is found that SMAD5-AS1 competitively bound to microRNA (miR)-106a-5p to regulate SMAD5. Herein, the study aimed to clarify the role of SMAD5-AS1/miR-106a-5p/SMAD5 axis in the process of epithelial mesenchymal transition (EMT) in NPC. SMAD5-AS1 was highly expressed and miR-106a-5p was poorly expressed in NPC tissues and cell lines. The NPC cells were treated with a series of small interfering RNAs, mimics, or inhibitors to explore the effects of SMAD5-AS1, SMAD5, and miR-106a-5p on EMT, cell proliferation, migration, and invasion in NPC. Of note, SMAD5-AS1 silencing or miR-106a-5p overexpression reduced expression of N-cadherin, matrix metallopeptidase 9, Snail, and Vimentin while elevating E-cadherin expression, thus inhibiting EMT, cell proliferation, migration, and invasion in NPC by down-regulation of SMAD5. Moreover, SMAD5 silencing could reduce the ability of EMT induced by SMAD5-AS1 up-regulation. SMAD5-AS1 silencing or miR-106a-5p elevation inhibited tumorigenesis in nude mice. Taken together, SMAD5-AS1 silencing suppressed EMT, cell proliferation, migration, and invasion in NPC by elevating miR-106a-5p to down-regulate SMAD5, which provided a novel therapeutic target for NPC treatment.-Zheng, Y.-J., Zhao, J.-Y., Liang, T.-S., Wang, P., Wang, J., Yang, D.-K., Liu, Z.-S. Long noncoding RNA SMAD5-AS1 acts as a microRNA-106a-5p sponge to promote epithelial mesenchymal transition in nasopharyngeal carcinoma.

Microwave hyperthermia enhances the sensitivity of lung cancer cells to gemcitabine through reactive oxygen species­induced autophagic death.

The pleiotropic effects of hyperthermia on cancer cells have been well documented, and microwave hyperthermia (MWHT) has been widely applied for multifarious cancer treatment. However, the mechanisms underlying the anticancer effect of MWHT combined with gemcitabine (GEM) remain poorly understood. The aim of the present study was to investigate the role of autophagy in the thermo­chemotherapy of human squamous cell lung carcinoma cells. It was observed that MWHT combined with GEM potently suppressed the viability of NCI­H2170 and NCI­H1703 cells, and induced G0/G1 cell cycle arrest. Notably, MWHT with GEM induced autophagy, as indicated by the formation of autophagic vacuoles, downregulation of p62 and upregulation of light chain 3­II. It was further demonstrated that the autophagy was due to the production of reactive oxygen species (ROS), whereas N­acetyl cysteine, an ROS scavenger, attenuated the level of autophagy. However, when the autophagy inhibitor 3­methyladenine was used, there was no significant change in the production of ROS. Furthermore, it was observed that MWHT combined with GEM downregulated the protein expression levels of phosphoinositide 3­kinase (PI3K), phosphorylated (p)­PI3K, protein kinase B (AKT), p­AKT, mammalian target of rapamycin (mTOR), p­mTOR, phosphorylated S6 (pS6) and p70 S6 kinase, which are associated with autophagy. In addition, the results demonstrated that ROS served as an upstream mediator of PI3K/AKT/mTOR signaling. In light of these findings, the present study provides original insights into the molecular mechanisms underlying the cell death induced by MWHT combined with GEM, and this may be a promising approach for the treatment of human squamous cell lung carcinoma.

MicroRNA-506 inhibits tumor growth and metastasis in nasopharyngeal carcinoma through the inactivation of the Wnt/ß-catenin signaling pathway by down-regulating LHX2.

BACKGROUND: Epithelial-mesenchymal transition (EMT)-associated proteins play key roles in cancer progression and metastasis with the involvement of microRNAs (miRNAs). This study aims to assess the role of miR-506 working in tandem with LIM Homeobox 2 (LHX2) in EMT and metastasis through the Wnt/ß-catenin signaling pathway in nasopharyngeal carcinoma (NPC). METHODS: Differentially expressed genes associated with NPC were screened using microarray analyses, from which LHX2 was identified. Next, the potential relationship between miR-506 and LHX2 was analyzed. In order to explore the effect of miR-506 or LHX2 on NPC cell proliferation, migration, invasion and apoptosis, serials of mimics, inhibitors or siRNA against LHX2 were transfected into NPC cells. Then, the expression patterns of LHX2, Wnt1, ß-catenin, E-cadherin, Vimentin, TCF4 and Twist were determined to assess the influence of miR-506 or LHX2 on EMT as well as the relationship between the Wnt/ß-catenin signaling pathway and TCF4. The tumorigenicity and lymph node metastasis (LNM) in xenograft tumors of nude mice were observed. RESULTS: The has-miR-506-3p was identified as the down-regulated gene in NPC based on the microarray data while LHX2 was negatively regulated by miR-506. Over-expression of miR-506 or silencing of LHK2 inhibited NPC cell proliferation, migration, invasion, tumorigenicity and LNM but promoted apoptosis indicated by decreased Wnt1, ß-catenin, Vimentin, TCF4 and Twist expressions along with increased E-cadherin expressions. CONCLUSIONS: miR-506 inhibits tumor growth and metastasis in NPC via inhibition of Wnt/ß-catenin signaling by down-regulating LHX2, accompanied by decreased TCF4. Taken together, miR-506 targeted-inhibition LHX2 presents a promising therapeutic strategy for the treatment of NPC. TRIAL REGISTRATION: ChiCTR1800018889 . Registered 15 October 2018.