lncRNA KLF3-AS1 Suppresses Cell Migration and Invasion in ESCC by Impairing miR-185-5p-Targeted KLF3 Inhibition.

Esophageal squamous cell carcinoma (ESCC) is a common cancer occurring in males and females worldwide. Accumulating evidence continues to highlight the crucial roles of long non-coding RNAs (lncRNAs) in the process of tumorigenesis. However, the regulatory mechanism of lncRNAs in ESCC remains unclear. The aim of this study is to elucidate the role of lncRNA Krüppel-like factor 3 antisense RNA 1 (KLF3-AS1) in ESCC by regulating miR-185-5p and KLF3. Initially, ESCC cell spheres with stem cell-like properties were prepared by suspension culture, and subsequently characterized by assessing colony formation ability and stem cell markers. LncRNA KLF3-AS1 was found to be poorly expressed in ESCC and could upregulate the expression of KLF3 by binding to miR-185-5p. lncRNA KLF3-AS1 upregulation was observed to inhibit miR-185-5p, thereby contributing to decreased expression of SOX2 and Oct4 (octamer-binding transcription factor 4). Furthermore, enhancement of lncRNA KLF3-AS1 resulted in reduced colony formation ability, cell invasion and migration, and tumor volume in vivo while promoting cell apoptosis in ESCC through downregulation of miR-185-5p. Collectively, this study indicated that lncRNA KLF3-AS1 inhibited ESCC cell invasion and migration by impairing miR-185-5p-mediated inhibition of KLF3, highlighting a promising novel potential target for ESCC treatment.

Side population cells from long-term passage non-small cell lung cancer cells display loss of cancer stem cell-like properties and chemoradioresistance.

The side population (SP) assay is a widely used method for isolating stem cell-like cells from cancer cell lines and primary cells. The cancer cells used in different laboratories have been passaged for different generations. Emerging evidence revealed that repeated passaging of cell lines for multiple generations frequently leads to change of characteristics. Thus, it is worth investigating the effects of repeated passaging on the biological and functional properties of the enriched SP fraction from early- and late-passage cells. The present study reports that the cancer stem cell (CSC) characteristics, including increased frequency of tumor-initiating and self-renewal capacity, and resistance to the chemotherapy agent doxorubicin and ionizing radiation, was diminished in SP cells from late-passage non-small cell lung cancer (NSCLC) cells. This finding revealed that the SP from long-term passage NSCLC cells was not consistently enriched for stem cell-like cancer cells, and low-passage cell lines and primary cancer cells are therefore recommended in the CSCs field.

Endoplasmic reticulum stress protects human thyroid carcinoma cell lines against ionizing radiation-induced apoptosis.

Radiotherapy is one of the most effective forms of cancer treatment, used in the treatment of a number of malignant tumors. However, the resistance of tumor cells to ionizing radiation remains a major therapeutic problem and the critical mechanisms determining radiation resistance are poorly defined. In the present study, a cellular endoplasmic reticulum (ER) stress microenvironment was established through the pretreatment of cultured thyroid cancer cells with tunicamycin (TM) and thapsigargin (TG), in order to mimic the ER stress response in a tumor microenvironment. This microenviroment was confirmed through the X­box binding protein 1 splice process, glucose­regulated protein 78 kD and ER degradation­enhancing α­mannosidase­like mRNA expression. A clonogenic assay was used to measure cancer cell resistance to 60Co­Î³ following TM pretreatment; in addition, human C/EBP homologous protein (CHOP) mRNA expression was determined and apoptosis assays were performed. The results showed that TM or TG pretreatment inhibited CHOP expression and reduced the apoptotic rate of cells. Furthermore, the results demonstrated that the induced ER stress response rendered cancer cells more resistant to ionizing radiation­induced apoptosis. Therefore, the ER stress pathway may be a potential therapeutic target in order to improve the clinical efficiency of radiotherapy.

[Mannatide enhances the efficacy of fractionated and unfractionated radiotherapy in mice bearing Lewis lung cancer].

OBJECTIVE: To investigate the effect of mannatide injection (MI) in enhancing the efficacy of radiotherapy in two therapeutic schedules in mice bearing Lewis lung cancer. METHODS: C57BL/6 mice bearing Lewis lung cancer xenograft were assigned randomly into control group, fractionated schedule (FS) group, nonfractionated schedule (NFS) group, MI group, FS+MI group, and NFS+MI group (n=10). MI (4.5 mg/kg) or saline was given intraperitoneally for 14 consecutive days in the corresponding groups. Radiation with 8 MeV electron beam was delivered in a single 4 Gy dose in NFS and in 4 fractions (total dose 4 Gy) in FS. Tumor inhibition rate and the spleen and thymus index were calculated after the treatments. RESULTS: MI significantly enhanced the efficacy of radiotherapy with a tumor inhibition rate reaching 70% in FS+MI group (P<0.01). FS resulted in a significantly higher tumor inhibition rate than NFS (P<0.05), but the rates were comparable between FS+MI and NFS+MI groups. The spleen index and thymus indices were significantly higher in FS+MI and NFS+MI groups than in FS and NFS groups (P<0.05). CONCLUSION: MI can enhance the efficacy of radiotherapy with different therapeutic schedules in mice bear Lewis lung cancer, and MI plus fractionated radiation produces the optimal effect.