Molecular mechanism of hyperoside inhibiting the biological behavior of nasopharyngeal carcinoma cells

doi:10.11958/20220805

Abstract

Abstract:

Objective To investigate the effect and mechanism of hyperoside on the biological behavior such as cell proliferation, migration and invasion of nasopharyngeal carcinoma cells. Methods SUNE1 cells were incubated with hyperin medium of 10 mg/L, 20 mg/L and 40 mg/L, and cells were divided into the low, the medium and the high dose groups. The lncRNA PAX8-AS1 overexpression or knockdown plasmid and miR-494-3p mimic were transfected into 40 mg/L hypericin-treated SUNE1 cells respectively. The activity, clonal formation, migration and invasion of SUNE1 cells were detected by CCK-8 assays, plate cloning experiment and Transwell assays. Western blot assay was used to analyze the expression of matrix metalloproteinase (MMP) -2 and MMP-9 proteins. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of long non-coding RNA (lncRNA) paired-box gene 8 antisense RNA 1 (PAX8-AS1) and miR-494-3p. Dual luciferase report experiment and RT-qPCR were used to determine the targeting relationship between lncRNA PAX8-AS1 and miR-494-3p. Results Low, medium and high dose-hyperoside significantly reduced the cell viability, migration number and invasion number of SUNE1 cells, and down-regulated expression levels of MMP-2 protein, MMP-9 protein and miR-494-3p, and up-regulated the expression level of lncRNA PAX8-AS1 (P<0.05). lncRNA PAX8-AS1 negatively regulated miR-494-3p expression. lncRNA PAX8-AS1 overexpression significantly enhanced inhibitory effects of 40 mg/L hyperoside on SUNE1 cell viability, migration and invasion, and MMP-2 and MMP-9 protein expression (P<0.05). Knockdown of lncRNA PAX8-AS1 and overexpression of miR-494-3p significantly reduced inhibitory effects of 40 mg/L hyperoside on SUNE1 cell viability, migration, invasion and MMP-2 and MMP-9 protein expression (P<0.05). Conclusion Hyperoside may inhibit the proliferation and migration, and invasion of nasopharyngeal carcinoma cells by up-regulating the lncRNA PAX8-AS1 /miR-494-3p axis.

Key words: nasopharyngeal neoplasms, molecular mechanisms of pharmacological action, genes, tumor suppressor, cell proliferation, neoplasm invasiveness, hyperoside, lncRNA PAX8-AS1, miR-494-3p

CLC Number:

R739.6

Figures/Tables 15

References 19

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组别	OD₄₅₀	细胞克隆数（个）
NC组	1.15±0.11	124.00±8.53
低剂量组	0.90±0.07^a	87.00±6.12^a
中剂量组	0.61±0.05^ab	62.00±4.57^ab
高剂量组	0.47±0.04^abc	47.00±2.88^abc
F	157.123^＊＊	292.522^＊＊

组别	OD₄₅₀	细胞克隆数（个）
NC组	1.15±0.11	124.00±8.53
低剂量组	0.90±0.07^a	87.00±6.12^a
中剂量组	0.61±0.05^ab	62.00±4.57^ab
高剂量组	0.47±0.04^abc	47.00±2.88^abc
F	157.123^＊＊	292.522^＊＊

组别	细胞迁移数量（个/视野）	细胞侵袭数量（个/视野）	MMP-2	MMP-9
NC组	234.00±16.73	164.00±9.17	0.81±0.07	0.78±0.07
低剂量组	189.00±12.37^a	131.00±8.02^a	0.68±0.06^a	0.65±0.05^a
中剂量组	138.00±9.47^ab	82.00±6.11^ab	0.50±0.05^ab	0.43±0.03^ab
高剂量组	91.00±7.54^abc	68.00±4.21^abc	0.42±0.03^abc	0.31±0.02^abc
F	238.698^＊＊	347.897^＊＊	93.655^＊＊	185.759^＊＊

组别	细胞迁移数量（个/视野）	细胞侵袭数量（个/视野）	MMP-2	MMP-9
NC组	234.00±16.73	164.00±9.17	0.81±0.07	0.78±0.07
低剂量组	189.00±12.37^a	131.00±8.02^a	0.68±0.06^a	0.65±0.05^a
中剂量组	138.00±9.47^ab	82.00±6.11^ab	0.50±0.05^ab	0.43±0.03^ab
高剂量组	91.00±7.54^abc	68.00±4.21^abc	0.42±0.03^abc	0.31±0.02^abc
F	238.698^＊＊	347.897^＊＊	93.655^＊＊	185.759^＊＊

组别	lncRNA PAX8-AS1	miR-494-3p
NC组	1.00±0.09	1.00±0.08
低剂量组	1.67±0.12^a	0.79±0.07^a
中剂量组	2.34±0.18^ab	0.58±0.04^ab
高剂量组	2.71±0.22^abc	0.40±0.03^abc
F	198.529^＊＊	175.891^＊＊