Exosomal circPVT1 promotes angiogenesis in laryngeal cancer by activating the Rap1b-VEGFR2 signaling pathway.

Laryngeal cancer (LC) is the second most common head and neck cancer and has a decreasing 5-year survival rate worldwide. Circular RNAs regulate cancer development in diverse ways based on their distinct biogenesis mechanisms and expansive regulatory roles. However, currently, there is little research on how exosomal circular RNAs are involved in the development of laryngeal cancer. Here, we demonstrated that circPVT1, a circular RNA derived from the well-studied long noncoding RNA PVT1, is correlated with disease progression in LC and promotes angiogenesis both in vivo and in vitro. Mechanistically, circPVT1 is loaded into LC cell-secreted exosomes and taken up by vascular epithelium cells. By sponging miR-30c-5p, exosomal circPVT1 promotes Rap1b expression, which dramatically enhances VEGFR2 and PI3K/AKT pathway activation, ultimately resulting in the induction of angiogenesis. Furthermore, our xenograft models demonstrated that the combination of shRNA-circPVT1 and cetuximab showed high efficacy in inhibiting tumor growth and angiogenesis. Collectively, these findings uncover a novel mechanism of exosomal circular RNA-mediated angiogenesis modulation and provide a preclinical rationale for testing this analogous combination in patients with LC.

Overexpression of the ASPM gene is associated with aggressiveness and poor outcome in bladder cancer.

Abnormal spindle-like microcephaly-associated (ASPM) protein is essential for mitotic spindle function during cell replication. The present study aimed to evaluate the hypothesis that ASPM serves a critical role in cancer invasiveness and may act as a prognostic biomarker in bladder cancer. In total, 6 independent worldwide bladder cancer microarray mRNA expression datasets (n=1,355) with clinical and follow-up annotations were collected from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Reverse transcription-quantitative polymerase chain reaction analysis revealed that ASPM mRNA expression was higher in bladder cancer tissue compared with adjacent normal bladder mucosae in 10 paired human tissue samples (P=0.004). ASPM overexpression in human bladder cancer samples was consistent with the mRNA expression datasets from GEO and TCGA. Bioinformatics analysis indicated that ASPM mRNA expression was significantly associated with grade and tumor node metastasis (TNM) stage in bladder cancer, based on pooled GEO and TCGA datasets (P<0.05). Stratification analysis indicated that the clinical significance of ASPM was particularly pronounced in low-grade or papillary subtypes of bladder cancer. Individual Cox and pooled Kaplan-Meier analyses suggested that ASPM expression was significantly directly correlated with poor overall (OS) and progression-free survival (PFS) in bladder cancer. Multivariate and stratification analyses demonstrated that the prognostic significance of ASPM was evident in low-grade or papillary bladder cancers, yet not in high-grade or non-papillary subgroups. Increased expression of ASPM was associated with poor OS in muscle-invasive bladder cancer and with poor PFS in non-muscle-invasive bladder cancer (P<0.05). Bioinformatics analysis identified the top 11 ASPM-related genes on STRING-DB.org. The expression of the majority of these genes was associated with poor outcomes of bladder cancer with statistical significance. Gene set enrichment analysis indicated that the high expression of ASPM could enrich gene signatures involved in mitosis, differentiation and metastasis in bladder cancer. Further analysis of TCGA datasets indicated that increased ASPM expression was significantly associated with higher Gleason score, T stage, N stage and poor clinical outcome in prostate cancer. It was also significantly associated with late TNM stage and poor PFS in renal cell carcinoma. In summary, ASPM may serve as a novel prognostic biomarker for low-grade or papillary bladder cancer.

[Distribution of neuropeptide Y-like immunoreactive fiber in rat temporomandibular joint].

OBJECTIVE: This investigation aimed at explore the total distribution of neuropeptide Y-like immunoreactive (NPY-LI) fibers and their changes post-trauma in rat temporomandibular joints (TMJs). METHODS: Six groups of rats were killed individually before trauma, 1, 3, 7, 14 and 28 days after trauma. TMJs were extracted totally, and the avidin-biotin-peroxidase complex method and image analysis were employed to detect NPY-LI fibers in frozen sections of TMJs. RESULTS: NPY-LI fibers were distributed extensively in TMJs, except the central disc band and bone, and they were mainly located around blood vessels, especially arteries. The densities of fibers in the six groups were 160.4 +/- 27.5, 95.8 +/- 16.4, 88.6 +/- 14.5, 114.3 +/- 17.0, 135.0 +/- 20.7, 158.6 +/- 19.5 (unit:mm2). CONCLUSION: NPY-LI nerve fibers are distributed extensively in the periphery of blood vessels of TMJs and densities changed dynamically when TMJs were impacted. NPY may play an important role in pathologic change of TMJ by regulating local blood circulation.