CircRNA hsa_circ_0070934 functions as a competitive endogenous RNA to regulate HOXB7 expression by sponging miR­1236­3p in cutaneous squamous cell carcinoma.

Circular ribonucleic acids (circRNAs) serve a vital role in the pathological processes of a number of diseases. Previous microarray results of circRNA expression revealed that hsa_circ_0070933 and hsa_circ_0070934, two circRNAs associated with the La ribonucleoprotein 1B gene, were highly expressed in cutaneous squamous cell carcinoma (CSCC). The present study aimed to explore the specific role of these circRNAs in CSCC. Through reverse transcription­quantitative PCR, hsa_circ_0070933 and hsa_circ_0070934 expression levels in CSCC cell lines and a human keratinocyte cell line were detected. Additionally, direct interactions between miR­1236­3p and HOXB7 or circ­0070934 were identified using RNA binding protein immunoprecipitation assays and dual­luciferase reporter assays. Cell Counting Kit­8, 5­ethynyl­2'­deoxyuridine, Transwell invasion and flow cytometry assays were used to assess the roles of miR­1236­3p or circ­0070934 in cell invasion, proliferation and apoptosis. Subsequently, in vivo tumor formation assays were used to verify the role of circ­0070934 in CSCC. The results demonstrated that the expression of circ­0070934 was stably upregulated in a number of CSCC cell lines compared with that in normal human keratinocytes. Knockdown of circ­0070934 inhibited the invasive and proliferative potential of CSCC cells and promoted apoptosis both in vivo and in vitro. In addition, circ­0070934 modulated HOXB7 expression through competitive binding with miR­1236­3p. In conclusion, the results of the present study demonstrated the effects of the circ­0070934/miR­1236­3p/HOXB7 regulatory axis on CSCC and provided a novel insight for the pathogenesis of CSCC.

PU.1-silenced dendritic cells prolong allograft survival in rats receiving intestinal transplantation.

AIM: To investigate the function of PU.1-silenced semi-mature dendritic cells (DCs) and the possibility of utilizing cell immunity in rat intestinal transplantation. METHODS: DCs were isolated from the bone marrow of F344 rats and cultured using the adherent method. The PU.1 gene was knocked down in DCs using small interfering RNAs (siRNAs) for 24 h, and the cells were then incubated with lipopolysaccharide for 48 h. The PU.1 siRNA that had the highest silencing efficiency was screened using reverse transcription-polymerase chain reaction and Western blot for further study. The tolerance capacity was analyzed and compared between PU.1-silenced DCs (siRNA PU.1 group), negative control-silenced DCs (siRNA NC group) and immature DCs (control group) both in vitro and in vivo. RESULTS: Blocking expression of the PU.1 gene in vitro led to a reduction in DC maturation and an increased tolerance capability. PU.1-silenced DCs expressed moderate levels of major histocompatibility complex (MHC)-II and low levels of co-stimulatory molecules, and produced more interleukin (IL)-10, but less IL-12. Compared with the negative control group, surface molecules cluster of differentiation 80 (CD80), CD86 and MHC-II in the siRNA PU.1 group were 27.0% ± 5.6%, 23.6% ± 4.8% and 36.8% ± 6.8%, respectively, and showed a significantly lower trend (P < 0.05). In vivo treatment of recipients with PU.1-silenced DCs injected before intestinal transplantation (siRNA PU.1 group), significantly prolonged allograft survival and resulted in better tissue histopathology compared with the siRNA NC group and control group. Mean survival time after transplantation was 14.3 ± 3.3 d in the siRNA PU.1 group (P < 0.05). CONCLUSION: PU.1-silenced semi-mature DCs induced partial immune tolerance both in vitro and in vivo, which could be used as a new strategy to promote transplantation tolerance.