Numerous studies have reported the association of long non-coding RNAs (lncRNAs) in cancers, yet the function of lncRNA high expressed in hepatocellular carcinoma (HEIH) in esophageal carcinoma (EC) has seldom been explored. Here, we aimed to explore the mechanism of HEIH on EC via microRNA-185 (miR-185)/kallikrein-related peptidase 5 (KLK5) modulation. Cancer and non-tumoral tissues were collected, in which HEIH, miR-185 and KLK5 expression were detected, as well as their correlations. Also, the relation between the prognosis of EC patients and HEIH/miR-185/KLK5 expression was clarified. EC cells (KYSE-30 and TE-1) were screened for subsequent gain- and loss-of-function assays and their biological functions were further monitored. Tumor volume and weight in EC mice were also measured. Results from this study indicated that HEIH and KLK5 were elevated and miR-185 was declined in EC. The positive correlation was seen in HEIH and KLK5 expression, while the negative correlation was observed in HEIH or KLK5 and miR-185 expression. High HEIH and KLK5 indicated worse prognosis and high miR-185 suggested better prognosis of EC patients. Depleting HEIH or restoring miR-185 suppressed the malignant phenotypes of EC cells, and delayed tumor growth in EC mice. HEIH was found to bind with miR-185 to regulate KLK5 expression. Overexpressing KLK5 alone promoted EC cell progression while up-regulating miR-185 reversed such effects on EC cells. Collectively, we reveal that HEIH depletion dampens EC progression by upregulating miR-185 and downregulating KLK5, which provides novel treatments for EC.
In this study, with the aid of microarray technology, transmembrane protease serine 4 (TMPRSS4), a novel member of the serine protease family, was found to be upregulated in the majority of lung adenocarcinoma (LUAD) tissues compared to normal lung tissues. Of note, the clinical significance of TMPRSS4 in LUAD has not yet been reported, at least to the best of our knowledge. Through immunohistochemistry assays, we found that TMPRSS4 was overexpressed in LUAD tissues and that the TMPRSS4 expression level was also proportionally associated with the AJCC clinical stage, T stage and pathological grade. Moreover, a high expression of TMPRSS4 was found to be associated with adverse outcomes and was a significant independent factors predicting a poor prognosis. To elucidate the possible mechanisms responsible for the overexpression of TMPRSS4, we examined at microRNAs (miRNAs or miRs), which are small non-coding RNAs commonly dysregulated in human malignancies and are known to promote carcinogenesis by interacting with other types of RNAs. By means of bioinformatics analysis, a miRNA potentially targeting TMPRSS4 mRNA, namely miR-125a-5p, was selected. Dual luciferase reporter gene assays were then performed to verify the interaction. The results of MTT assays and apoptotic assays revealed that miR-125a-5p significantly inhibited cell growth and enhanced apoptosis, and the silencing of TMPRSS4 had similar effects. Furthermore, we observed that either the overexpression of miR-125a-5p or the silencing of TMPRSS4 prevented the activation of the nuclear factor (NF)-κB signaling pathway. On the whole, our findings illustrate that TMPRSS4 may be a candidate oncogene and may thus serve as a prognostic biomarker for LUAD, and its overexpression may be partly ascribed to the downregulation of miR-125a-5p. The dysregulation of miR-125a-5p and TMPRSS4 affect the biological function of LUAD cells via the NF-κB signaling pathway. The miR-125a-5p/TMPRSS4/NF-κB axis may thus provide novel insight into the pathogenic mechanisms of LUAD and may be used in the development of novel treatment strategies for LUAD.
PC is often diagnosed at an advanced stage leaving no effective therapies. At present, the 5-year relative survival rate of PC is about 8%, ranking lowest amongst all cancers. 1,2 The reasons for the poor survival and high mortality of PC are multi-factorial including the close proximity of surrounding important tissues and its special tumour microenvironment. 3,4 Although surgical resection remains the
Studies have shown that bone marrow-derived cells play an important role in tumor recurrence after chemotherapy and radiotherapy. In this study, we examined the relationship between the accumulation of Gr-1+CD11b+ cells and tumor recurrence after irradiation in tumor-bearing mice. By transplanting bone marrow cells into whole body-irradiated mice depleted of bone marrow, we assessed the role of Gr-1+CD11b+ cells in lung carcinoma models after local irradiation (LI). 20 Gy local irradiation could recruit CD11b+CXCR4+ cells into the irradiated tissues, and the recruited CD11b+CXCR4+ cells could promote tumor recurrence. Further 6 Gy whole body irradiation (WBI6Gy) could decrease tumor recurrence by inhibiting the accumulation of Gr-1+CD11b+ cells and then suppressing tumor vasculogenesis and angiogenesis. Our results suggest that the accumulation of CD11b+Gr-1+ cells promote tumor re-growth after local irradiation by enhancing tumor neovascularization, and low dose of whole body irradiation or irradiation of enlarged spleen may provide a new alternative for anti-angiogenesis therapies.
Livin, a member of the inhibitor of apoptosis protein (IAP) family, is expressed at a high level in lung adenocarcinoma and influences the progression of cancer, and its response to chemotherapy and radiotherapy. Aberrant microRNA (miRNA) expression has also been associated with cancer initiation and development. However, the clinical significance of Livin and its relationship with miRNAs in lung adenocarcinoma are still unclear. In the present study, the expression level of Livin in 90 pairs of lung adenocarcinoma and their adjacent tissues were detected by immunohistochemistry staining. Spearman correlation and Kaplan-Meier, univariate and multivariate analyses were applied to evaluate the correlation between the expression of Livin and clinical characteristics. With the integration of bioinformatics analysis and dual-luciferase reporter gene assays, we identified the miRNA that can target Livin mRNA. The functional effects of miRNA-mediated Livin knockdown were assessed by Cell Counting Kit-8 (CCK-8) and apoptosis assays, and cell cycle analysis. The present study revealed that Livin was upregulated in lung adenocarcinoma tissues and may be associated with the poor prognosis in lung adenocarcinoma patients. The overexpression of Livin is partly caused by the downregulation of miR-198. Further exploration revealed that miRNA-198-mediated silencing of Livin significantly inhibited cell growth and enhanced apoptosis of A549 cells, accompanied by marked upregulation of caspase-3. Finally, we observed that the miR-198 overexpression and Livin neutralization had similar effects on improving cisplatin chemosensitivity in A549 cells. Overall, these findings suggest that Livin has the potential to become a biomarker for predicting the prognosis of lung adenocarcinoma and may provide a promising strategy for assisting chemotherapy of lung adenocarcinoma through the miR-198/Livin/caspase-3 regulatory network.
Long noncoding RNAs (lncRNAs) have emerged as regulators of gene expression and play critical regulatory roles in diverse biological functions and diseases, including cancer. In this study, we report the downregulation of LINC01089 in non-small cell lung cancer (NSCLC) samples, relative to adjacent non-tumor tissues, and demonstrate its role in the inhibition of proliferation, migration, and epithelial–mesenchymal transition (EMT) of NSCLC cells. Mechanistic analysis indicates that LINC01089 acts as a sponge for miR-27a, regulating its expression in NSCLC. Interestingly, LINC01089 mediated the upregulation of SFRP1 expression by inhibiting the Wnt/β-catenin–EMT pathway and inhibiting the epithelial–mesenchymal transition of NSCLC via sponging miR-27a. Overall, our findings highlight LINC01089’s tumorigenic role and regulatory mechanism in NSCLC, thereby suggesting its potential as a therapeutic target for managing NSCLC.
Purpose: Long noncoding RNAs (lncRNAs) are emerging as gene regulators to drive many important cancer phenotypes through interaction with microRNAs. There have been numerous data about upregulation of H19 and its strong oncogenic function in progression of cancers. However, the function and detailed mechanisms of H19 on small cell lung cancer (SCLC) are still unclear. Methods: In this study, we investigated H19 expression in SCLC and para-carcinoma tissues. We also explored the function and detailed mechanisms of H19 on SCLC cells via RT-PCR, transwell assay, Western blot, dual-luciferase report assay and RNA pull-down experiments.Results: In this study, we observed that H19 was upregulated in SCLC compared with paracarcinoma tissues or NSCLC tissues. We also uncovered that H19 could promote proliferation and migration of SCLC cells. Functional investigation illustrated that H19 acted as a sponge for miR-140-5p to regulate its expression in SCLC. Interestingly, we further found that H19 upregulated FGF9 expression to promote SCLC progression via sponging miR-140-5p. H19 and FGF9 were also revealed to have similar expression patterns in clinical SCLC samples. Conclusion: These data demonstrated that H19 might be a promising prognostic and therapeutic target for SCLC.
Conditional survival rate (CSR) is defined as the dynamic possibility of survival, considering the changes in the survival risk over time. The present study aimed to compare the CSR of the surgical procedures for stage IA1 non-small cell lung cancer (NSCLC). Overall, data for 2,535 patients with stage IA1 NSCLC after lobectomy, segmentectomy or wedge resection were obtained from the Surveillance, Epidemiology and End Results database, and the overall survival (OS) rates were subsequently compared. CSR estimates, the possibility of patients who had already survived x years, to survive further y years, was calculated as CSR=S(x+y)/S(x), where S is the survival rate at a particular point in time. A Cox regression model and propensity-score matching were used to adjust confounding factors. There were no statistical differences in the OS among the three surgical procedures, except that OS of patients who underwent a lobectomy was improved compared with the wedge resection. The CSR of surviving to the 5th year after operation improved gradually over time. The 3-year CSR of lobectomy or segmentectomy was higher compared with that of the wedge resection. Moreover, the 3-year CSR of segmentectomy was higher compared with that of lobectomy from the 3rd year after surgery, particularly in some specific situations, such as female sex, patients ≥66 years old, patients with squamous cell carcinoma or patients with poor tumor differentiation. The present study is the first report to compare CSR following lobectomy, segmentectomy and wedge resection for patients with stage IA1 NSCLC, to the best of our knowledge. These findings indicated that lobectomy is the most conservative surgical procedure for stage IA1 NSCLC and raises questions regarding improved long-term prognosis of segmentectomy in some subsets of patients. XIAOXI FAN, YICHENG LIANG, YUNPENG BAI, CHUNLU YANG and SHUN XU
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