Macrocyclization of bisindole quinolines regarding selective stabilizing of Gquadruplex DNA structures

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. 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, we 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. www.selleckchem.com/btk.html 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).