Long Noncoding RNA MIR210HG is Induced by Hypoxia-inducible Factor 1α and Promotes Cervical Cancer Progression

Background：Increasing evidence has indicated that long noncoding RNAs (lncRNAs) play essential roles in various types of cancer, especially the ability of tumor cells to adapt to hypoxia conditions. However, only a few of them have been experimentally validated in cervical squamous cell carcinoma (CSCC). Method: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to confirm the expression of MIR210HG in CSCC tissues compared with matched non-tumor tissues, and analyze its clinical significance. In vitro, RNA interference (siRNA) or overexpression plasmid was used to investigate the biological function and underlying mechanism of MIR210HG in cervical carcinogenesis. In vitro, cell proliferation and metastasis were evaluated by Cell Counting Kit-8 (CCK-8) and transwell assay, respectively. Furthermore, tumor growth and metastasis were evaluated in vivo using a xenogenous subcutaneously implant or a pulmonary metastasis model. Immunohistochemical staining or immunoblotting analysis was carried out to detect protein expression.Results：In the current study, we identified a hypoxia-induced lncRNA MIR210HG was excessively expressed in CSCC tissues and regulated by human papillomavirus (HPV) type 16 E6 and E7 via hypoxia-inducible factor 1α (HIF-1α). Functional assays revealed the role of MIR210HG in promoting proliferation, migration and invasion of CSCC cells in vitro under normoxia as well as hypoxia conditions. Meanwhile, stable MIR210HG silencing dramatically repressed tumor growth and pulmonary metastasis in vivo. Mechanistically, the depletion of MIR210HG or HIF-1α decreased each other’s expression level, while silencing MIR210HG or HIF-1α respectively downregulated the expression levels of phosphoglycerate kinase 1 (PGK1), one of key metabolic enzymes in the glycolysis pathway. Furthermore, decreased expression of PGK1 by HIF-1α knockdown was reversed through the overexpression of MIR210HG. Also, we demonstrated HIF-1α can activate the transcription of MIR210HG via binding its promoter. Conclusions: Taken together, these results expand our understanding of the cancer-associated functions of hypoxia-induced lncRNAs, and highlight MIR210HG forms a feedback loop with HIF-1α contributing to cervical carcinogenesis, with potential implications for therapeutic targeting.

Preliminary study of CT features of intermediate- and high-grade alimentary lymphoma and adenocarcinoma in cats

Case series summary The ultrasonographic findings of many feline intestinal tumours are similar. This study evaluated the CT features of intermediate- and high-grade alimentary lymphoma and adenocarcinoma in cats. CT was performed on six cats with adenocarcinoma and 14 cats with lymphoma. Comparisons between tumour types were conducted, focusing on CT features, including obstruction (present or absent), growth patterns of lesions (symmetry or asymmetry), layering enhancement (present or absent), location of the lesion, number of lesions (solitary or multiple), lymphadenopathy (present or absent), location of lymphadenopathy, pulmonary metastasis (present or absent) and maximum thickness (mm) of the lesion. The cats with adenocarcinoma (n = 5/6 [83%]) experienced intestinal obstruction significantly more often than cats with lymphoma (n = 0/14 [0%]; P = 0.0004). Layering enhancement was observed significantly more often in cats with adenocarcinoma (n = 6/6 [100%]) than in cats with lymphoma (n = 1/14 [7%]; P = 0.0002). Lymphadenopathy was detected significantly more often in cats with lymphoma (n = 14/14 [100%]) than in cats with adenocarcinoma (n = 2/6 [33%]) ( P = 0.003). In cats with lymphoma, the intestine (12.1 ± 3.9 mm) was significantly thicker than that in cats with adenocarcinoma (6.4 ± 2.3 mm; P = 0.005). Relevance and novel information To the best of our knowledge, no reports have described the characteristics of feline intestinal tumours using CT. Layering enhancement was observed in cats with intestinal adenocarcinomas. No layering enhancement was observed in alimentary lymphoma in cats, but enlarged regional nodes were noted. Lesions with lymphoma were thicker than those with adenocarcinoma. These findings may help differentiate between adenocarcinomas and lymphomas.