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Jinjin Sun*, Zhijia Jiang*, Yanxun Li, Kaiqiang Wang, Xing Chen, Geng Liu Department of Hepatopancreatobiliary Surgery, The Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinjin SunDepartment of Hepatopancreatobiliary Surgery, The Second Hospital of Tianjin Medical University, No. 23 Ping-Jiang Road, Hexi District, Tianjin 300211, People’s Republic of ChinaTel +86 1 862 205 7820Fax +86 8 832 8331Email jsun02@tmu.edu.cnBackground: MicroRNA (miR)-21 is overexpressed in numerous types of malignancy and participates in the development of cancer. However, the basic mechanism of the influence of miR-21 on the malignant phenotype of pancreatic cancer remains unclear.Purpose: The present study aimed to investigate the role of miR-21 in pancreatic cancer development and explore its molecular mechanism.Patients and methods: The tissue samples were collected at the Second Hospital of Tianjin Medical University (Tianjin, China) between January 2013 and December 2015. The expression of VHL in tissue samples was evaluated by IHC staining. The expression of miR-21 was measured by quantitative real-time polymerase chain reaction (qRT-PCR). MiR-21 target gene was detected by real-time PCR, Western blot and the luciferase reporter assay. Cell viability, cell proliferation, cell migration and invasion were evaluated by the MTT assays, the colony formation assays and the transwell assays. The nude mouse tumor xenograft model was performed to detect the effect of miR-21 on tumor growth in vivo.Results: Von Hippel-Lindau tumor suppressor (VHL) was downregulated in pancreatic cancer tissues compared with pancreatic non-tumor tissues. VHL was identified as a novel direct target of miR-21, by which it is negatively regulated. In PANC-1 cells, inhibition of miR-21 and upregulation of VHL significantly suppressed cell proliferation, migration and invasion. Knockdown of miR-21 inhibited the hypoxia-inducible factor (HIF)-1α/vascular endothelial growth factor (VEGF) pathway, while inhibiting the expression of matrix metallopeptidase (MMP)-2 and MMP-9. Silencing of miR-21 inhibited tumor growth in vivo.Conclusion: Knockdown miR-21 increased the expression of VHL, and thus modulated the HIF-1α/VEGF pathway and the expression of MMP-2 and MMP-9, which led to the inhibition of the proliferation, migration and invasion of pancreatic cancer cells. All of these results suggest that the miR-21/VHL interaction may be a novel potential target for pancreatic cancer prevention and therapy.Keywords: miR-21, pancreatic cancer, VHL, proliferation, migration, invasion

Trampling by grazing animals exerts a comprehensive and serious effect on grassland vegetation and soil. In order to compare the trampling of yaks and Tibetan sheep under different grazing intensities, we examined the hoof pressure and trampling intensity (based on trampling area and hoof-print count) of white yaks (Poephagus grunniens) and Tibetan sheep (Ovis ammon) in an alpine meadow of Tianzhu County, Gansu Province, China, under conditions where either grazing area or livestock number were controlled. The average areas trampled by yaks and Tibetan sheep were 39.2 and 21.6 cm2 respectively. The average hoof pressure of yaks and Tibetan sheep were 6.89 and 3.13 kg cm–2 respectively. The yak-to-sheep ratio of the average area trampled was 1.81:1, whereas the yak-to-sheep ratio of average hoof pressure was 2.20:1. Average ingestion and walking trampling intensities of yaks were 384.8 × 103 and 247.1 × 103 kg cm–2, respectively, in controlled grazing areas, and 439.1 × 103 and 756.3 × 103 kg cm–2, respectively, in areas of controlled livestock numbers. These values for Tibetan sheep were 15.3 × 103 and 120.3 × 103 kg cm–2 in controlled grazing areas, and 42.6 × 103 and 128.2 × 103 kg cm–2 in areas of controlled livestock numbers. In controlled grazing areas, the ingestion and walking trampling intensities of yaks were 25.2 and 5.4 times higher, respectively, than those of sheep. Under areas of controlled livestock numbers, these values were 10.3 and 5.9 times higher, respectively, than those of sheep. The average trampling intensity of yaks was 7.3 times higher than that of the sheep. Therefore, under conditions of similar grazing intensity, yaks cause more damage than Tibetan sheep in alpine meadows.