Winklerdamm3846
ls via directly acting on miR-127-3p/MDM2 axis. Our findings may provide novel perspectives for the treatment of NSCLC in patients resistant to chemotherapy.
Genetic and epigenetic alterations have been indicated to be closely correlated with the carcinogenesis, DNA methylation is one of most frequently occurring molecular behavior that take place early during this complicated process in gastric cancer (GC).
In this study, 398 samples were collected from the cancer genome atlas (TCGA) database and were analyzed, so as to mine the specific DNA methylation sites that affected the prognosis for GC patients. Moreover, the 23,588 selected CpGs that were markedly correlated with patient prognosis were used for consistent clustering of the samples into 6 subgroups, and samples in each subgroup varied in terms of M, Stage, Grade, and Age. In addition, the levels of methylation sites in each subgroup were calculated, and 347 methylation sites (corresponding to 271 genes) were screened as the intrasubgroup specific methylation sites. Meanwhile, genes in the corresponding promoter regions that the above specific methylation sites were located were performed signaling pattely predicting patient prognosis.
Long non-coding RNAs (lncRNAs) are a class of endogenous non-coding RNAs of longer than 200bp that play crucial roles in cancer biology. Here, we assessed the tumorigenic properties of a long noncoding RNA, MIAT, in non-small cell lung cancer (NSCLC).
Survival and clinicopathological analyses were done in a cohort of 80 patients with NSCLC. MIAT expression level were determined by real-time quantitative reverse transcriptase PCR (qRT-PCR). #link# Dual luciferase reporter assays were employed to test the interaction between MIAT and miR-149-5p. Ectopic overexpression and shRNA-mediated knockdown of MIAT, CCK-8 and colony formation assays, Transwell migration and invasion in vitro, and in vivo tumorigenesis experiment were used to evaluate the function of MIAT.
MIAT was significantly up-regulated in NSCLC tissues and cell lines, and was closely associated with advanced pathological stage and poor overall survival. Gain- and loss-of-function experiments in cell lines and mouse xenograft models showed that MIAT promoted the proliferation, migration, and invasion of NSCLC cells in vitro and accelerated tumor growth in vivo. Luciferase assay, western blotting, qRT-PCR, and rescue experiments showed that, mechanistically, MIAT could directly bind to miR-149-5p, and subsequently served as a sponge to increase the expression level of Forkhead box M1 (FOXM1).
Our study reveals that MIAT acts as an oncogene in NSCLC via a novel MIAT/miR-149/FOXM1 axis, thus providing potential biomarkers and therapeutic targets for the management of NSCLC.
Our study reveals that MIAT acts as an oncogene in NSCLC via a novel MIAT/miR-149/FOXM1 axis, thus providing potential biomarkers and therapeutic targets for the management of NSCLC.Human AlkB homolog H5 (ALKBH5) is a primary m6A demethylase, which is dysregulated and acts as a biological and pharmacological role in human cancers or non-cancers. ALKBH5 plays a dual role in various cancers through regulating kinds of biological processes, such as proliferation, migration, invasion, metastasis and tumor growth. In addition, it takes a great part in human non-cancer, including reproductive system diseases. The underlying regulatory mechanisms of ALKBH5 that relys on m6A-dependent modification are implicated with long non-coding RNA, cancer stem cell, autophagy and hypoxia. ALKBH5 is also an independent prognostic indicator in various cancers. In this review, we summarized the current evidence on ALKBH5 in diverse human cancers or non-cancers and its potential as a prognostic target.
Colorectal cancer (CRC) is one of the most common digestive malignant tumors in the world. Ubiquitin-specific peptidase 18 (USP18) plays a regulatory role in tumorigenesis, and abnormal expression of Snail1 is also believed to be related to tumorigenesis. However, whether USP18 could affect colorectal cancer through Snail1 remains unclear. This study was designed to investigate the role of USP18 in colorectal cancer.
USP18 protein and mRNA abundance in clinical tissues and five cell lines were analyzed with quantitative real-time PCR (qRT-PCR) and western blot. link2 USP18 overexpression-treated DLD1 cells and USP18 knockdown-treated SW480 cells were used to study cell proliferation, migration, invasion, and the expression of epithelial-mesenchymal transformation (EMT) biomarkers. Moreover, ubiquitination-related Snail1 degradation was detected with qRT-PCR and western blot. The relationships between USP18 and Snail1 were investigated with western blot, co-immunoprecipitation, migration, and invasion.
USP18 was highly expressed in colorectal cancer tissues. Overexpression of USP18 could promote proliferation, colony formation, migration, and invasion of colorectal cancer cells. Overexpression of USP18 effectively promoted cell survival after treatment with three different chemotherapy drugs. Moreover, USP18 could regulate Snail1 degradation through ubiquitination pathway. Furthermore, we demonstrated that Snail1 could effectively reverse the influence of USP18 on cell proliferation, migration, invasion, and EMT of CRC cells.
USP18 could promote the proliferation, migration, and invasion of colorectal cancer by deubiquitinating and stabilizing the Snail1 protein in colorectal cancer.
USP18 could promote the proliferation, migration, and invasion of colorectal cancer by deubiquitinating and stabilizing the Snail1 protein in colorectal cancer.
Meningiomas are the second most common primary tumors of the central nervous system. However, there is a paucity of data on meningioma biology due to the lack of suitable preclinical in vitro and in vivo models. In this study, we report the establishment and characterization of patient-derived, spontaneously immortalized cancer cell lines derived from World Health Organization (WHO) grade I and atypical WHO grade II meningiomas.
We evaluated high-resolution 3T MRI neuroimaging findings in meningioma patients which were followed by histological analysis. RT-qPCR and immunostaining analyses were performed to determine the expression levels of meningioma-related factors. Additionally, flow cytometry and sorting assays were conducted to investigate and isolate the CD133 and CD44 positive cells from primary atypical meningioma cells. Further, we compared the gene expression profiles of meningiomas and cell lines derived from them by performing whole-exome sequencing of the blood and tumor samples from the patients, and the primary cancer cell lines established from the meningioma tumor.
Our results were consistent with earlier studies that reported mutations in
,
, and
genes in atypical meningiomas, and we also observed mutations in
, a gene that was recently discovered. Significantly, the genomic signature was consistent between the atypical meningioma cancer cell lines and the tumor and blood samples from the patient.
Our results lead us to conclude that established meningioma cell lines with a genomic signature identical to tumors might be a valuable tool for understanding meningioma tumor biology, and for screening therapeutic agents to treat recurrent meningiomas.
Our results lead us to conclude that established meningioma cell lines with a genomic signature identical to tumors might be a valuable tool for understanding meningioma tumor biology, and for screening therapeutic agents to treat recurrent meningiomas.
Concurrent chemoradiotherapy is the common first-line treatment for patients with advanced cervical cancer. However, radioresistance remains a major clinical challenge, which results in recurrence and poor survival. Many studies have shown the potential of Delta-like Ligand 4 (DLL4) as a novel prognostic biomarker and therapeutic target in many solid tumors. Previously, Tucatinib clinical trial have found that high DLL4 expression in tumor cells may predict the pelvic lymph node metastasis and poor prognosis in patients with cervical cancer. In our present study, we further studied the effects of DLL4 on the biological behavior and radiosensitivity of cervical cancer cells.
The expression of DLL4 and epithelial-mesenchymal transition (EMT) phenotype markers in cervical cancer cell lines or tissues were detected using Western blotting, and the expression of DLL4 mRNA in cervical cancer cell lines or tissues was detected using Quantitative real-time PCR. The effect of DLL4 on cell proliferation, migration, and radiosensitivity wd metastasis of cervical cancer and its potential as a predictive biomarker for radiosensitivity and prognosis in patients with cervical cancer patients receiving concurrent chemoradiotherapy (cCRT).
Downregulation of DLL4 inhibited the progression and increased the radiosensitivity in cervical cancer cells by reversing EMT. These results indicated the promising prospect of DLL4 against the radioresistance and metastasis of cervical cancer and its potential as a predictive biomarker for radiosensitivity and prognosis in patients with cervical cancer patients receiving concurrent chemoradiotherapy (cCRT).
Long non-coding RNAs (lncRNAs) play significant roles in tumorigenesis and can contribute to identification of novel therapeutic targets for cancers. This paper was aimed at exploring the role of CTBP1 divergent transcript (CTBP1-AS2) in cervical cancer (CC) progression.
qRT-PCR and western blot assays were used to detect relevant RNA and protein expressions. In vitro functional assays, including CCK8, EdU, TUNEL and transwell assays were applied to explore the functions of CTBP1-AS2 in CC cell proliferation, apoptosis and migration. In vivo animal study was utilized to investigate the role of CTBP1-AS2 in tumor growth. Luciferase reporter, RNA pull down and RIP assays were performed to determine the specific mechanical relationship between CTBP1-AS2, miR-3163 and ZNF217.
CTBP1-AS2 was significantly overexpressed in CC cell lines. Knockdown of CTBP1-AS2 curbed cell proliferation, migration and invasion, while stimulated cell apoptosis in vitro. CTBP1-AS2 facilitated xenograft tumor growth in vivo. Cytoplasmic CTBP1-AS2 was found to be a miR-3163 sponge in CC cells. MiR-3163 inhibition abolished the anti-tumor effects of CTBP1-AS2 knockdown. Additionally, Zinc finger protein 217 (ZNF217) was identified as a direct target of miR-3163. link3 CTBP1-AS2 acted as a miR-3163 sponge to elevate ZNF217 expression. ZNF217 up-regulation abrogated the tumor suppressing effects of CTBP1-AS2 knockdown.
CTBP1-AS2 regulates CC progression via sponging miR-3163 to up-regulate ZNF217.
CTBP1-AS2 regulates CC progression via sponging miR-3163 to up-regulate ZNF217.
Aberrant methylation and miRNA-target-gene regulation function as important mechanisms for gene inactivation in colon carcinogenesis. Although a serious of molecular events (such as aberrant alterations of genomics and epigenetics) have been identified to be related to prognostic in colon cancer (CC) patients, beneficial biomarkers for early diagnosis and prognostic evaluation remain largely unknown.
In our study, the role of NEURL1B, including gene expression analysis, methylation characteristic, miRNA-target regulation, diagnostic and prognostic significance, were evaculated using multiple bioinformatic tools based on TCGA database and clinical samples.
Our data showed that NEURL1B was aberrantly downregulated in CC, regardless of the mRNA level or protein level. Moreover, ROC curve and multivariate Cox regression analysis demonstrated that NEURL1B was adiagnostic and independent prognostic facter for CC patients. Of interest, methylation of NEURL1B was also high and closely associated with poor survival in CC.
