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1. 南昌大学第一附属医院泌尿外科,江西 南昌 330006
2. 南昌大学第一附属医院病理科,江西 南昌 330006
Received:07 October 2021,
Revised:2021-11-25,
Published:30 January 2022
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Kunyang LEI, Wenjie XIE, Ting SUN, et al. Expression and effect of long non-coding RNA ARAP1-AS1 in clear cell renal cell carcinoma[J]. China Oncology, 2022, 32(1): 34-40.
Kunyang LEI, Wenjie XIE, Ting SUN, et al. Expression and effect of long non-coding RNA ARAP1-AS1 in clear cell renal cell carcinoma[J]. China Oncology, 2022, 32(1): 34-40. DOI: 10.19401/j.cnki.1007-3639.2022.01.004.
背景与目的:
长链非编码RNA(long non-coding RNA
lncRNA)ARAP1-AS1在多种肿瘤中异常表达
但其在肾
透明细胞癌(clear cell renal cell carcinoma
ccRCC)中的作用尚不清楚。探讨ARAP1-AS1在ccRCC中的生物学作用。
方法:
通过GEPIA数据库分析ARAP1-AS1在ccRCC组织中的表达及其与临床病理学特征及患者生存率的关系。采用实时荧光定量聚合酶链反应(real-time fluorescence quantitative polymerase chain reaction
RTFQ-PCR)检测ccRCC组织及邻近的非肿瘤组织中ARAP1-AS1的表达水平。将患者分为ARAP1-AS1高表达组和低表达组
分析ARAP1-AS1的表达水平与患者临床病理学特征之间的关系
并进行生存分析。通过细胞计数试剂盒-8(cell counting kit-8
CCK-8)实验、transwell迁移实验及侵袭实验检测ARAP1-AS1对ccRCC细胞体外增殖、迁移及侵袭能力的影响。采用蛋白质印迹法(Western blot)检测Wnt/
&
#x003b2;-catenin信号通路相关蛋白表达变化。采用BALB/c裸小鼠移植瘤模型分析ARAP1-AS1对ccRCC细胞体内成瘤能力的影响。
结果:
GEPIA数据库分析结果显示
ARAP1-AS1在ccRCC中高表达
且与患者肿瘤高分期及较差的生存率相关(
P
均
<
0.05)。RTFQ-PCR显示
ARAP1-AS1在ccRCC组织及细胞系中高表达
ARAP1-AS1的高表达与肿瘤大小和分期相关(
P
均
<
0.05)。ARAP1-AS1高表达患者的总生存率较差(
P
<
0.05)。沉默ARAP1-AS1的表达可以抑制ccRCC细胞增殖、迁移和侵袭(
P
均
<
0.05)。沉默ARAP1-AS1可以降低Wnt/
&
#x003b2;-catenin信号通路相关蛋白的表达水平(
P
均
<
0.05)。沉默ARAP1-AS1可使ccRCC细胞体内成瘤能力减弱
并使Ki-67增殖指数降低。
结论:
ARAP1-AS1可通过激活Wnt/
&
#x003b2;-catenin信号通路促进ccRCC的进展。
Background and purpose:
Long non-coding RNA (lncRNA) ARAP1-AS1 is abnormally expressed in a variety of tumors
but its role in clear cell renal cell carcinoma (ccRCC) is unknown. This study aimed to explore the biological role of ARAP1-AS1 in ccRCC.
Methods:
The expression level of ARAP1-AS1 in ccRCC tissues and its relationship to patient
&
#x02019;s clinicopathological characteristics and survival rate were analyzed using the GEPIA database. The expression level of ARAP1-AS1 was measured in ccRCC and adjacent non-tumor tissues by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR). Patients were divided into ARAP1-AS1 high and low expression groups
the relationship between ARAP1-AS1 expression level and patient
&
#x02019;s clinicopathological characteristics was analyzed
and survival analysis was performed. The effect of ARAP1-AS1
in vitro
proli
feration
migration and invasion ability of ccRCC cells was determined by cell counting kit-8 (CCK-8) assay
transwell migration and invasion assay. Changes in the expressions of Wnt/
&
#x003b2;-catenin signaling pathway-related proteins were detected by Western blot assay. The effect of ARAP1-AS1 on tumorigenic capacity in ccRCC cells
in vivo
was verified by tumor xenografts in nude mice.
Results:
The analysis of the GEPIA database showed that ARAP1-AS1 was highly expressed in ccRCC and associated with advanced tumor stage as well as poor survival in patients (all
P
<
0.05). The results of RTFQ-PCR showed that ARAP1-AS1 was highly expressed in ccRCC tissues and cell lines
and high expression correlated with tumor size and stage (all
P
<
0.05). The overall survival rate was poor in patients with high ARAP1-AS1 expression (
P
<
0.05). Knockdown of ARAP1-AS1 expression inhibited the proliferation
migration and invasion of ccRCC cells (all
P
<
0.05). Silencing of ARAP1-AS1 reduced the expression levels of the proteins involved in the Wnt/
&
#x003b2;-catenin signaling pathway (all
P
<
0.05). Silencing of ARAP1-AS1 attenuated tumorigenic capacity in ccRCC cells and reduced Ki-67 proliferation index (
P
<
0.05).
Conclusion:
ARAP1-AS1 promotes ccRCC progression through activation of the Wnt/
&
#x003b2;-catenin signaling pathway.
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