circRNA-CHD2 promoting metastasis of pancreatic cancer via miR-30e-3p/MDM2/TP53 axis

doi:10.3877/cma.j.issn.1674-0793.2022.01.003

Abstract

Abstract:

Objective

To reveal the mechanisms of circRNA-CHD2 promoting the metastasis of pancreatic cancer.

Methods

Kaplan-Meier curve was used to analyze the correlation between the expression of circRNA-CHD2 and the clinicopathological characteristics and prognosis of pancreatic cancer. The effect of circRNA-CHD2 on invasion and metastasis of pancreatic cancer cell line was analyzed by scratch test and Transwell test. Bioinformatics analysis, RNA pull-down assay and qPCR method were used to confirm the binding of circRNA-CHD2 and miR-30e-3p.

Results

There was a significantup-regulation of circRNA-CHD2 in pancreatic cancer tissues compared to tumor-adjacent tissues (P<0.01). Up-regulation of circRNA-CHD2 was correlated with poor prognosis of patients with pancreatic cancer. Functional tests showed that circRNA-CHD2 could promote pancreatic cancer cell metastasis in vitro. Mechanistically, circRNA-CHD2 functioned as a miR-30e-3p endogenous sponge and targetedmiR-30e-3p/MDM2/TP53 axis.

Conclusions

circRNA-CHD2 can promote metastasis of pancreatic cancer by regulating miR-30e-3p/MDM2/TP53 axis. Therefore, circRNA-CHD2 may serve as a prognostic biomarker and therapeutic target in pancreatic cancer.

Key words: Pancreatic neoplasms, Circular RNA, circRNA-CHD2, miR-30e-3p, MDM2

Bowen Gao, Yuming Luo, Yao Kong, Dingwen Zhang, Yiyao Ya, Jiabin Yang, Xing He, Wenbin Li. circRNA-CHD2 promoting metastasis of pancreatic cancer via miR-30e-3p/MDM2/TP53 axis[J]. Chinese Archives of General Surgery(Electronic Edition), 2022, 16(01): 14-19.

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URL: https://zhptwkxwx.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-0793.2022.01.003

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Figures/Tables 6

References 15

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引物名称	序列（5’→3’）
circRNA-CHD2上游引物	TCACACAACCTTCACCCTCA
circRNA-CHD2下游引物	AGGACCCTGAGATCGCTTTG
GAPDH上游引物	CACATCGCTCAGACACCATG
GAPDH下游引物	TGACGGTGCCATGGAATTTG
CHD2上游引物	AAGCTTCGGGTTCAGACTCA
CHD2下游引物	CTCTTTGGCTTCTGGGAGGA
MDM2上游引物	ATGGGAGGCGTGTTCAGTAA
MDM2下游引物	GCAGCAGAGATGTGGGATTG
TP53上游引物	GATTTGATGCTGTCCCCGGA
TP53下游引物	GCACCACCACACTATGTCGA
miR-4778-3p	TGCTCTTCTTCCTTTGCAGAGTTGA
miR-5196-3p	TTCATCCTCGTCTCCCTCCCAG
miR-30e-3p	GCCTTTCAGTCGGATGTTTACAGC
miR-520a-5p	GACGCTCCAGAGGGAAGTACTTTCT
miR-525-5p	ATCGCTCCAGAGGGATGCACTTTCT
miR-6072	ATCGGTCCTCATCACACTGCACCTTAG
miR-20a-3p	CGCCGGACTGCATTATGAGCACTTAAAG
miR-124-3p	GCTAAGGCACGCGGTGAATGCCAA
miR-134-3p	CTGTGGGCCACCTAGTCACCAA

引物名称	序列（5’→3’）
circRNA-CHD2上游引物	TCACACAACCTTCACCCTCA
circRNA-CHD2下游引物	AGGACCCTGAGATCGCTTTG
GAPDH上游引物	CACATCGCTCAGACACCATG
GAPDH下游引物	TGACGGTGCCATGGAATTTG
CHD2上游引物	AAGCTTCGGGTTCAGACTCA
CHD2下游引物	CTCTTTGGCTTCTGGGAGGA
MDM2上游引物	ATGGGAGGCGTGTTCAGTAA
MDM2下游引物	GCAGCAGAGATGTGGGATTG
TP53上游引物	GATTTGATGCTGTCCCCGGA
TP53下游引物	GCACCACCACACTATGTCGA
miR-4778-3p	TGCTCTTCTTCCTTTGCAGAGTTGA
miR-5196-3p	TTCATCCTCGTCTCCCTCCCAG
miR-30e-3p	GCCTTTCAGTCGGATGTTTACAGC
miR-520a-5p	GACGCTCCAGAGGGAAGTACTTTCT
miR-525-5p	ATCGCTCCAGAGGGATGCACTTTCT
miR-6072	ATCGGTCCTCATCACACTGCACCTTAG
miR-20a-3p	CGCCGGACTGCATTATGAGCACTTAAAG
miR-124-3p	GCTAAGGCACGCGGTGAATGCCAA
miR-134-3p	CTGTGGGCCACCTAGTCACCAA

临床病理特征		例数	低表达	高表达	χ²值	P值
例数		82	41	41
性别					1.297	0.254
	男	51	23	28
	女	31	18	13
年龄（岁）					1.231	0.267
	≤60	45	25	20
	>60	37	16	21
分化程度					0.236	0.889
	低	31	15	16
	中	27	13	14
	高	24	13	11
淋巴转移					7.312	0.007^b
	无	23	17	6
	有	59	24	35
TNM分期					9.938	0.034^a
	Ⅰ	12	9	3
	Ⅱ	57	29	28
	Ⅲ	13	3	10

临床病理特征		例数	低表达	高表达	χ²值	P值
例数		82	41	41
性别					1.297	0.254
	男	51	23	28
	女	31	18	13
年龄（岁）					1.231	0.267
	≤60	45	25	20
	>60	37	16	21
分化程度					0.236	0.889
	低	31	15	16
	中	27	13	14
	高	24	13	11
淋巴转移					7.312	0.007^b
	无	23	17	6
	有	59	24	35
TNM分期					9.938	0.034^a
	Ⅰ	12	9	3
	Ⅱ	57	29	28
	Ⅲ	13	3	10

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