KIAA1522对肺癌细胞增殖、迁移和侵袭的影响及其机制

doi:10.13481/j.1671-587X.20250317

Abstract

Abstract:

Objective To discuss the effect of KIAA1522 on the proliferation， migration， and invasion of lung cancer cells， and to clarify its signaling mechanism. Methods Bioinformatics analysis was used to detect the expression levels of KIAA1522 mRNA and protein in 75 cases of human non-small cell lung cancer （NSCLC） tissues and adjacent normal lung tissues； immunohistochemical staining was used to detect the expression of KIAA1522 protein in NSCLC tissue and adjacent normal lung tissues； Western blotting method was used to detect the expression level of KIAA1522 protein in various lung cancer cell lines. KIAA1522-small interfering（siRNA） and over-expression plasmids were transfected into the lung cancer H1299 and A549 cells， respectively. The KIAA1522-siRNA experiment was divided into blank group， negative control group （si-NC group）， KIAA1522-siRNA#1 group， and KIAA1522-siRNA#2 group. The KIAA1522 over-expression experiment was divided into control group， empty vector control group （OE-NC group， transfected with KIAA1522 over-expression empty vector plasmid）， KIAA1522 overexpression group （OE-KIAA1522 group， transfected with KIAA1522 over-expression plasmid）， KIAA1522 over-expression+MK2206 group ［OE-KIAA1522+MK2206 group， co-transfected with KIAA1522 over-expression plasmid and protein kinase B （AKT） signaling pathway inhibitor MK2206］， and MK2206 group （transfected with MK2206）. Western blotting method was used to verify the transfection efficiencies of the cells in various groups； MTT assay was used to detect the proliferation activities of the lung cancer cells in various groups； cell scratch assay was used to detect the migration rates of lung cancer cells in various groups； Transwell chamber assay was used to detect the numbers of invasion lung cancer cells in various groups； Western blotting method was used to detect the expression levels of phosphorylated AKT （p-AKT）， total AKT （t-AKT）， cyclin D1 （Cyclin D1）， vascular endothelial growth factor （VEGF）， and epithelial-mesenchymal transition （EMT）-related proteins ［vimentin （Vimentin）， N-cadherin （N-cadherin）， and E-cadherin （E-cadherin）］ proteins in the cells in various groups. Results The bioinformatics analysis results showed that compared with adjacent normal lung tissue， the expression levels of KIAA1522 mRNA and protein in NSCLC tissue were significantly increased （P<0.05 or P<0.01）. The immunohistochemistry staining results showed that compared with adjacent normal lung tissue， the positive expression rate of KIAA1522 protein in NSCLC tissue was significantly increased （P<0.05） and was associated with TNM stage （P<0.01）. The Western blotting results showed that compared with normal lung epithelial cells BEAS-2B， the expression levels of KIAA1522 protein in lung cancer cell lines PC9， H1299， H460， A549， H1975， and H226 were significantly increased （P<0.05 or P<0.01）. Compared with si-NC group， the expression levels of KIAA1522 protein in the H1299 cells in KIAA1522-siRNA#1 group and KIAA1522-siRNA#2 group were significantly decreased （P<0.01）； compared with OE-NC group， the expression level of KIAA1522 protein in the A549 cells in OE-KIAA1522 group was significantly increased （P<0.01）. The MTT results showed that at 24， 48， and 72 h of cell culture， compared with si-NC group， the proliferation activities of the H1299 cells in KIAA1522-siRNA#1 group and KIAA1522-siRNA#2 group were significantly decreased （P<0.01）； compared with OE-NC group， the proliferation activity of the A549 cells in OE-KIAA1522 group was significantly increased （P<0.05）； compared with OE-KIAA1522 group， the proliferation activity of the A549 cells in OE-KIAA1522+MK2206 group was significantly decreased （P<0.01）； compared with OE-KIAA1522+MK2206 group， the proliferation activity of the A549 cells in MK2206 group was significantly decreased （P<0.05）. The cell scratch assay results showed that compared with si-NC group， the migration rates of the H1299 cells in KIAA1522-siRNA#1 group and KIAA1522-siRNA#2 group were significantly decreased （P<0.01）； compared with OE-NC group， the migration rate of the A549 cells in OE-KIAA1522 group was significantly increased （P<0.01）； compared with OE-KIAA1522 group， the migration rate of the A549 cells in OE-KIAA1522+MK2206 group was significantly decreased （P<0.05）； compared with OE-KIAA1522+MK2206 group， the migration rate of the A549 cells in MK2206 group was significantly decreased （P<0.05）. The Transwell chamber assay results showed that compared with si-NC group， the numbers of invasion H1299 cells in KIAA1522-siRNA#1 group and KIAA1522-siRNA#2 group were significantly decreased （P<0.01）； compared with OE-NC group， the number of invasion A549 cells in OE-KIAA1522 group was significantly increased （P<0.01）； compared with OE-KIAA1522 group， the number of invasion A549 cells in OE-KIAA1522+MK2206 group was significantly decreased （P<0.01）； compared with OE-KIAA1522+MK2206 group， the number of invasion A549 cells in MK2206 group was significantly decreased （P<0.01）. The Western blotting results showed that compared with si-NC group， the expression levels of p-AKT， Cyclin D1， Vimentin， N-cadherin， and VEGF proteins in the H1299 cells in KIAA1522-siRNA#1 group and KIAA1522-siRNA#2 group were significantly decreased （P<0.05 or P<0.01）， while the expression level of E-cadherin protein was significantly increased （P<0.01）； compared with OE-NC group， the expression levels of p-AKT， Cyclin D1， Vimentin， N-cadherin， and VEGF proteins in the A549 cells in OE-KIAA1522 group were significantly increased （P<0.05 or P<0.01）， while the expression level of E-cadherin protein was significantly decreased （P<0.05）； compared with OE-KIAA1522 group， the expression levels of p-AKT， Cyclin D1， Vimentin， N-cadherin， and VEGF proteins in the A549 cells in OE-KIAA1522+MK2206 group were significantly decreased （P<0.05 or P<0.01）， while the expression level of E-cadherin protein was significantly increased （P<0.05）； compared with OE-KIAA1522+MK2206 group， the expression levels of Cyclin D1， Vimentin， N-cadherin， and VEGF proteins in the A549 cells in MK2206 group were significantly decreased （P<0.05 or P<0.01）， while the expression level of E-cadherin protein was significantly increased （P<0.05）. Conclusion The KIAA1522 protein upregulates the expression of Cyclin D1， EMT-related proteins， and VEGF protein in lung cancer cells， promoting the proliferation， migration， and invasion of lung cancer cells， and its mechanism is related to the activation of the AKT signaling pathway.

Key words: KKIAA1522, Carcinoma， non-small-cell lung, Protein kinase B, Cell proliferation, Cell invasion

CLC Number:

R734.2

Yihui WANG,Qing ZHANG,Yingnan LI,Liping YE. Effect of KIAA1522 on proliferation, migration, and invasion of lung cancer cells and its mechanism[J].Journal of Jilin University(Medicine Edition), 2025, 51(3): 727-739.

Figures/Tables 13

Fig. 1

Fig. 2

Tab. 1

Expressions of KIAA1522 protein in cancer tissue of NSCLC patients with different clinicopathological characteristics"

Clinicopathological characteristic	n	KIAA1522		$χ 2$	P
Clinicopathological characteristic	n	＋	－	$χ 2$	P
Age
≤60	33	26	7	0.251	0.616
>60	42	31	11	0.251	0.616
Gender
Male	43	32	11	0.488	0.485
Female	32	26	6	0.488	0.485
Maximum diameter of tumor（cm）
≤3	34	24	10	1.614	0.204
>3	41	34	7	1.614	0.204
Differentiation
Well-moderate	51	42	9	2.291	0.130
Poor	24	16	8	2.291	0.130
TNM stage
Ⅰ	31	18	13	11.192	0.001
Ⅱ+Ⅲ	44	40	4	11.192	0.001
Lymphnode metastasis
Yes	2	2	0		1.000
No	73	56	17	-	1.000

Tab. 1

Fig. 3

Fig. 4

Fig. 5

Tab.2

Tab.3

Fig. 6

Fig. 7

Fig. 8

Fig. 9

Fig. 10

References 25

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Group	Proliferation activity
Group	（t/h）	24	48	72
Si-NC		0.146±0.008	0.200±0.009	0.278±0.010
KIAA1522-siRNA#1		0.095±0.010^*	0.161±0.001^*	0.224±0.007^*
KIAA1522-siRNA#2		0.089±0.010^*	0.156±0.011^*	0.204±0.004^*

Group	Proliferation activity
Group	（t/h）	24	48	72
OE-NC		0.138±0.012	0.216±0.006	0.330±0.007
OE-KIAA1522		0.150±0.016^*	0.255±0.014^*	0.388±0.011^*
OE-KIAA1522+MK2206		0.129±0.007^△	0.191±0.013^△	0.300±0.012^△
MK2206		0.118±0.011^#	0.158±0.007^#	0.261±0.004^#

Effect of KIAA1522 on proliferation, migration, and invasion of lung cancer cells and its mechanism

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