ABSTRACT
PURPOSE: A substantial amount of evidence demonstrates suggests that long non-coding RNAs (lncRNAs) play a key role in the progression of various malignancies, cervical squamous cell carcinoma (CSCC) included. In our study, we deeply investigated the role and molecular mechanism of lncRNA NPHS2-6 in CSCC. METHODS: The expression level of gene and protein expression were measured by qRT-PCR and western blot. To test the cell proliferation and cell metastasis ability, we carried out the CCK-8 experiment, clone formation assay, transwell assay and wound healing, respectively. The interactivity among NPHS2-6, miR-1323 and SMC1B were co demonstrated using the bioinformatics tool, dual-luciferase reporter system, and RNA pulldown assay. The subcutaneous tumor model of nude mice was established to verify the results of previous studies at the in vivo. NPHS2-6 was upregulated in CSCC tissues and cells. RESULTS: NPHS2-6 deficiency significantly inhibited CSCC cell growth and EMT in vitro. In addition, NPHS2-6 deficiency also inhibited the growth of CSCC xenograft tumors in mice in vivo. Importantly, NPHS2-6 was a competing endogenous RNA (ceRNA) to increases SMC1B levels by binding to miR-1323, leading to activate the PI3K/Akt pathway, thereby exacerbating tumorigenesis of CSCC. CONCLUSIONS: In conclusion, NPHS2-6/miR-1323/SMC1B/PI3K/Akt signaling accelerates the progression of CSCC, providing a new direction for the treatment strategy of CSCC.
Subject(s)
Carcinoma, Squamous Cell , MicroRNAs , Uterine Cervical Neoplasms , Female , Humans , Animals , Mice , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Mice, Nude , Cell Line, Tumor , Uterine Cervical Neoplasms/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Cell Proliferation/genetics , Cell Movement/genetics , Gene Expression Regulation, NeoplasticABSTRACT
Aim: Cutaneous squamous cell carcinoma (cSCC) is a common disease in patients exposed to UV-light and human papillomavirus. Electrochemotherapy, a well-established treatment modality with minimum side effects in human and veterinary medicine, circumvents chemoresistance to bleomycin by the use of electric fields. However, patients are sensitive to the trauma produced by the insertion of the needles that lengthen recovery times, particularly cats with nasal planum cSCC. To address this matter, we developed thin-needles electrodes. Methods: Thin-needles electrodes developed using computer simulations and plant tissue models were compared to standard electrodes. A prospective non-randomized study recruiting 52 feline patients with nasal planum cSCC was performed. Local response, anorexia, and overall survival were evaluated. Results: Computer simulations and plant model experiments showed satisfactory results with both electrodes. The patients treated with the thin-needle electrode obtained similar local response rates compared to the standard group, OR 97.3% vs. 80%, respectively (P < 0.067). Most patients in the thin-needle group resumed eating in less than 48 h, as the anorexia was significantly lower (P < 0.0001). Using the standard electrode, most patients took 3 to 5 days to resume normal feeding. The electric current circulating in the standard electrode was 44% higher, contributing to a longer duration of anorexia due to tissue damage. The overall survival in both groups was similar. Conclusion: Electrochemotherapy using thin-needle electrodes provides equivalent local response rates and overall survival compared with standard electrodes but significantly reduced return to appetite after the treatment. These results may be useful in the development of new electrodes for human patients.