Expression of protein arginine methyltransferase 5 in lung cancer and its mechanism of promoting lung cancer

doi:10.3969/j.issn.1674-8115.2021.08.003

Abstract

Abstract: Objective

·To investigate the expression of protein arginine methyltransferase 5 (PRMT5) in lung cancer and its effect on proliferation, migration and invasion of lung cancer cells.

Methods

· Immunohistochemistry was used to detect the expression of PRMT5 in 73 pairs of lung cancer tissues and adjacent tissues, and its correlation with clinical characteristics of patients was analyzed. After PRMT5 was down-regulated in lung cancer cell line NCI-H1299, the effects of PRMT5 on cell proliferation, migration and invasion were observed by CCK8 assay and Transwell chamber, and the expressions of E-cadherin, vimentin and transcription factor SNAI1 were detected by Western blotting. The expression of PRMT5 in tumor cell lines and lung cancer tissues was analyzed by using the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database, respectively, and the relationship between the expression of PRMT5 in tissues and the prognosis of lung cancer patients was further analyzed.

Results

·Immunohistochemistry showed that the expression of PRMT5 in lung cancer tissues was significantly higher than that in adjacent tissues (P=0.000), and the expression of PRMT5 in stage Ⅲ?Ⅳ was higher than that in stage Ⅰ?Ⅱ (P=0.033). After PRMT5 down-regulation, the proliferation, migration and invasion ability of NCI-H1299 cells decreased, the expression of E-cadherin increased and the expression of vimentin and SNAI1 decreased. The lung cancer sequencing data of TCGA database showed that the expression of PRMT5 in lung cancer tissues was significantly higher than that in normal lung tissues, and the lung adenocarcinoma patients and the lung squamous cell carcinoma patients with higher expression of PRMT5 had lower overall survival rate (P=0.005) and relapse-free survival rate (P=0.028), respectively.

Conclusion

· PRMT5 is highly expressed in lung cancer tissues, which can promote the proliferation, migration and invasion of lung cancer cells. High expression of PRMT5 is associated with poor prognosis of lung cancer.

Key words: protein arginine methyltransferase 5 (PRMT5), lung cancer, proliferation, migration, epithelial-mesenchymal transition (EMT)

CLC Number:

R734.2

Bing-qian ZHOU, Li HAN, Zhe-yi CHEN, Shi-yu CHEN, Ying-xia ZHENG. Expression of protein arginine methyltransferase 5 in lung cancer and its mechanism of promoting lung cancer[J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(8): 1009-1016.

Figures/Tables 9

TrendMD

References 17

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Intensity of PRMT5 expression	Proportion of PRMT5-positive cells	Score
Negative	0	0
Weakly positive	0‒25%	1
Moderately positive	25%‒50%	2
Strongly positive	50%‒75%	3
No stronger intensity	75%‒100%	4

Intensity of PRMT5 expression	Proportion of PRMT5-positive cells	Score
Negative	0	0
Weakly positive	0‒25%	1
Moderately positive	25%‒50%	2
Strongly positive	50%‒75%	3
No stronger intensity	75%‒100%	4

shRNA	Sequence （5′→3′）
NC-shRNA	F： GATCTGTTCTCCGAACGTGTCACGTTTCAAGAGAACGTGACACGTTCGGAGAATTTTTTC
	R： AATTCAAAAAATTCTCCGAACGTGTCACGTTCTCTTGAAACGTGACACGTTCGGAGAACA
PRMT5-shRNA1	F： GATCCGCCCAGTTTGAGATGCCTTATTTCAAGAGAATAAGGCATCTCAAACTGGGCTTTTTTG
	R： AATTCAAAAAAGCCCAGTTTGAGATGCCTTATTCTCTTGAAATAAGGCATCTCAAACTGGGCG
PRMT5-shRNA2	F： GATCCGGCTGACCTCCCATCTAATCATTCAAGAGATGATTAGATGGGAGGTCAGCCTTTTTTG
	R： AATTCAAAAAAGGCTGACCTCCCATCTAATCATCTCTTGAATGATTAGATGGGAGGTCAGCCG
PRMT5-shRNA3	F： GATCCCCCATCCTCTTCCCTATTAAGCTTCCTGTCAGACTTAATAGGGAAGAGGATGGGTTTTTG
	R： AATTCAAAAACCCATCCTCTTCCCTATTAAGTCTGACAGGAAGCTTAATAGGGAAGAGGATGGGG

shRNA	Sequence （5′→3′）
NC-shRNA	F： GATCTGTTCTCCGAACGTGTCACGTTTCAAGAGAACGTGACACGTTCGGAGAATTTTTTC
	R： AATTCAAAAAATTCTCCGAACGTGTCACGTTCTCTTGAAACGTGACACGTTCGGAGAACA
PRMT5-shRNA1	F： GATCCGCCCAGTTTGAGATGCCTTATTTCAAGAGAATAAGGCATCTCAAACTGGGCTTTTTTG
	R： AATTCAAAAAAGCCCAGTTTGAGATGCCTTATTCTCTTGAAATAAGGCATCTCAAACTGGGCG
PRMT5-shRNA2	F： GATCCGGCTGACCTCCCATCTAATCATTCAAGAGATGATTAGATGGGAGGTCAGCCTTTTTTG
	R： AATTCAAAAAAGGCTGACCTCCCATCTAATCATCTCTTGAATGATTAGATGGGAGGTCAGCCG
PRMT5-shRNA3	F： GATCCCCCATCCTCTTCCCTATTAAGCTTCCTGTCAGACTTAATAGGGAAGAGGATGGGTTTTTG
	R： AATTCAAAAACCCATCCTCTTCCCTATTAAGTCTGACAGGAAGCTTAATAGGGAAGAGGATGGGG

Primer	Forward （5’→3’）	Reverse （5’→3’）
PRMT5	CGATCAGACCTACTGCTGTCA	CTCGGAGTTCCTGCGAATCT
β-actin	CATGTACGTTGCTATCCAGGC	CTCCTTAATGTCACGCACGAT
VIM	GACGCCATCAACACCGAGTT	CTTTGTCGTTGGTTAGCTGGT
SNAI1	TCGGAAGCCTAACTACAGCGA	AGATGAGCATTGGCAGCGAG
CDH1	ATTTTTCCCTCGACACCCGAT	TCCCAGGCGTAGACCAAGA