lncRNA MIF-AS1调节miR-423-5p/PYCR1轴对前列腺癌细胞恶性生物学行为的影响

doi:10.3969/j.issn.1006-5725.2024.18.006

Abstract

Abstract:

Objective To investigate the effect of long non-coding RNA （lncRNA） macrophage migration inhibitory factor antisense RNA1 （MIF-AS1） on the malignant biological behavior of prostate cancer （PC） cells by regulating the miR-423-5p/pyrroline-5-carboxylic acid reductase 1 （PYCR1） axis. Methods PC3 cells were cultured in vitro to knock down the expression of MIF-AS1 or down-regulate the expression of miR-423-5p. The expression of MIF-AS1， miR-423-5p and PYCR1 mRNA in tumor tissues and adjacent tissues and cells of PC patients were detected. The cell proliferation， apoptosis， migration， and invasion were detected and the expression of PYCR1 protein was detected by Western blot. The relationships between miR-423-5p， IF-AS1 and PYCR1 were verified. Results The MIF-AS1 and PYCR1 mRNA were observed to be highly expressed in the tumor tissues， while miR-423-5p was lowly expressed. Silenced MIF-AS1 inhibited the proliferation， migration and invasion of PC3 cells and up-regulated miR-423-5p induced cell apoptosis （P < 0.05）. Inhibition of miR-423-5p expression reversed the inhibitory effect of silencing MIF-AS1 on malignant behavior of PC3 cells （P < 0.05）. miR-423-5p was correlated with MIF-AS1 and PYCR1 by targeted regulation. Conclusion Silencing MIF-AS1 may inhibit the expression of PYCR1 by up-regulating miR-423-5p， thereby inhibiting the malignant behavior of PC cells.

Key words: long non-coding RNA macrophage migration inhibitory factor antisense RNA1, miR-423-5p, pyrroline-5-carboxylic acid reductase 1, prostate cancer, malignant biological behavior

CLC Number:

R737.31

Jianbo YANG,Jichun SHAO,Zhijun ZENG,Tao ZHAO,Xing. WANG. Effect of lncRNA MIF⁃AS1 on the malignant biological behavior of prostate cancer cells by regulating the miR⁃423⁃5p/PYCR1 axis[J]. The Journal of Practical Medicine, 2024, 40(18): 2544-2549.

Figures/Tables 11

Tab.1

Tab.2

Tab.3

Tab.4

Fig.1

Tab.5

Fig.2

Tab.6

Fig.3

Fig.4

Fig.5

References 26

1	RAFIKOVA G， GILYAZOVA I， ENIKEEVA K， et al. Prostate Cancer： Genetics， Epigenetics and the Need for Immunological Biomarkers［J］. Int J Mol Sci， 2023， 24（16）：12797. doi:10.3390/ijms241612797 doi: 10.3390/ijms241612797
2	BERGENGREN O， PEKALA K R， MATSOUKAS K， et al. 2022 Update on Prostate Cancer Epidemiology and Risk Factors-A Systematic Review［J］. Eur Urol， 2023， 84（2）：191-206. doi:10.1016/j.eururo.2023.04.021 doi: 10.1016/j.eururo.2023.04.021
3	SEKHOACHA M， RIET K， MOTLOUNG P， et al. Prostate Cancer Review： Genetics， Diagnosis， Treatment Options， and Alternative Approaches［J］. Molecules， 2022， 27（17）：5730-5742. doi:10.3390/molecules27175730 doi: 10.3390/molecules27175730
4	WU M， HUANG Y， CHEN T， et al. LncRNA MEG3 inhibits the progression of prostate cancer by modulating miR-9-5p/QKI-5 axis［J］. J Cell Mol Med， 2019， 23（1）：29-38. doi:10.1111/jcmm.13658 doi: 10.1111/jcmm.13658
5	TAN Y T， LIN J F， LI T， et al. LncRNA-mediated posttranslational modifications and reprogramming of energy metabolism in cancer［J］. Cancer Commun （Lond）， 2021， 41（2）：109-120. doi:10.1002/cac2.12108 doi: 10.1002/cac2.12108
6	LI L， LI Y， HUANG Y， et al. Long non-coding RNA MIF-AS1 promotes gastric cancer cell proliferation and reduces apoptosis to upregulate NDUFA4［J］. Cancer Sci， 2018， 109（12）：3714-3725. doi:10.1111/cas.13801 doi: 10.1111/cas.13801
7	WANG B， ZHANG Y， YE M， et al. Cisplatin-resistant MDA-MB-231 Cell-derived Exosomes Increase the Resistance of Recipient Cells in an Exosomal miR-423-5p-dependent Manner［J］. Curr Drug Metab， 2019， 20（10）：804-814. doi:10.2174/1389200220666190819151946 doi: 10.2174/1389200220666190819151946
8	FERRI C， DI BIASE A， BOCCHETTI M， et al. MiR-423-5p prevents MALAT1-mediated proliferation and metastasis in prostate cancer［J］. J Exp Clin Cancer Res， 2022， 41（1）：20-32. doi:10.1186/s13046-021-02233-w doi: 10.1186/s13046-021-02233-w
9	KAY E J， PATERSON K， RIERA-DOMINGO C， et al. Cancer-associated fibroblasts require proline synthesis by PYCR1 for the deposition of pro-tumorigenic extracellular matrix［J］. Nat Metab， 2022， 4（6）：693-710. doi:10.1038/s42255-022-00582-0 doi: 10.1038/s42255-022-00582-0
10	张丽红，胡良峰，杨烨，等. PYCR1在肝癌中的表达特点及其临床价值［J］. 医学研究杂志， 2023， 52（2）：76-80.
11	SCHATTEN H. Brief overview of prostate cancer statistics， grading， diagnosis and treatment strategies［J］. Adv Exp Med Biol， 2018， 1095（1）：1-14.
12	VIETRI M T， D'ELIA G， CALIENDO G， et al. Hereditary prostate cancer： Genes related， target therapy and prevention［J］. Int J Mol Sci， 2021， 22（7）：3753-3762. doi:10.3390/ijms22073753 doi: 10.3390/ijms22073753
13	MCCABE E M， RASMUSSEN T P. lncRNA involvement in cancer stem cell function and epithelial-mesenchymal transitions［J］. Semin Cancer Biol， 2021， 75（1）：38-48. doi:10.1016/j.semcancer.2020.12.012 doi: 10.1016/j.semcancer.2020.12.012
14	HAGHIGHI R， CASTILLO-ACOBO R Y， AMIN A H， et al. A thorough understanding of the role of lncRNA in prostate cancer pathogenesis； Current knowledge and future research directions［J］. Pathol Res Pract， 2023， 248：154666. doi:10.1016/j.prp.2023.154666 doi: 10.1016/j.prp.2023.154666
15	YANG G， LI T， LIU J， et al. lncRNA MAGI2-AS3 suppresses castration-resistant prostate cancer proliferation and migration via the miR-106a-5p/RAB31 axis［J］. Genomics， 2023， 115（2）：110599. doi:10.1016/j.ygeno.2023.110599 doi: 10.1016/j.ygeno.2023.110599
16	NI P， WANG G， WANG Y， et al. Correlation of MIF-AS1 polymorphisms with the risk and prognosis of gastric cancer［J］. Pathol Res Pract， 2022， 233（1）：153-163. doi:10.1016/j.prp.2022.153850 doi: 10.1016/j.prp.2022.153850
17	FAN Y， WANG L， HAN X C， et al. LncRNA MIF-AS1 aggravates the progression of ovarian cancer by sponging miRNA-31-5p［J］. Eur Rev Med Pharmacol Sci， 2020， 24（5）：2248-2255.
18	GUO Y， ZHOU X， GAO F， et al. MiR-423-5p is a novel endogenous control for the quantification of circulating miRNAs in human esophageal squamous cell carcinoma［J］. Heliyon， 2023， 9（4）：e14515. doi:10.1016/j.heliyon.2023.e14515 doi: 10.1016/j.heliyon.2023.e14515
19	WANG Q， WANG L X， ZHANG C Y， et al. LncRNA CRNDE promotes cell proliferation， migration and invasion of ovarian cancer via miR-423-5p/FSCN1 axis［J］. Mol Cell Biochem， 2022， 477（5）：1477-1488. doi:10.1007/s11010-022-04382-8 doi: 10.1007/s11010-022-04382-8
20	JIANG F， HU X， CAO H， et al. Hsa_circ_0000081 promotes the function of gastric cancer through sponging hsa-miR-423-5p to influence 3-phosphoinositide-dependent kinase 1 expression［J］. Bioengineered， 2022， 13（4）：8277-8290. doi:10.1080/21655979.2022.2053796 doi: 10.1080/21655979.2022.2053796
21	XUE S T， ZHENG B， CAO S Q， et al. Long non-coding RNA LINC00680 functions as a ceRNA to promote esophageal squamous cell carcinoma progression through the miR-423-5p/PAK6 axis［J］. Mol Cancer， 2022， 21（1）：69-78. doi:10.1186/s12943-022-01539-3 doi: 10.1186/s12943-022-01539-3
22	SHANG Y， WANG L， ZHU Z， et al. Downregulation of miR-423-5p Contributes to the Radioresistance in Colorectal Cancer Cells［J］. Front Oncol， 2021， 10（1）：582-590. doi:10.3389/fonc.2020.582239 doi: 10.3389/fonc.2020.582239
23	CUI B， HE B， HUANG Y， et al. Pyrroline-5-carboxylate reductase 1 reprograms proline metabolism to drive breast cancer stemness under psychological stress［J］. Cell Death Dis， 2023， 14（10）：682. doi:10.1038/s41419-023-06200-5 doi: 10.1038/s41419-023-06200-5
24	程秋华，周帅，向杨，等. PYCR1基因在肝细胞癌中的表达及与预后的关系［J］. 实用医学杂志， 2021， 37（2）：233-237.
25	DU S， SUI Y， REN W， et al. PYCR1 promotes bladder cancer by affecting the Akt/Wnt/β-catenin signaling［J］. J Bioenerg Biomembr， 2021， 53（2）：247-258. doi:10.1007/s10863-021-09887-3 doi: 10.1007/s10863-021-09887-3
26	XU H， HE Y， LIN L， et al. MiR-1207-5p targets PYCR1 to inhibit the progression of prostate cancer［J］. Biochem Biophys Res Commun， 2021， 575：56-64. doi:10.1016/j.bbrc.2021.08.037 doi: 10.1016/j.bbrc.2021.08.037

目的基因	引物序列（5′→3′）
MIF?AS1	上游：ACATCGGCATGATGGCAGAA
MIF?AS1	下游：TCACAAAAGGCGGGACCAC
miR?423?5p	上游：TGAGGGGCAGAGAGCGA
miR?423?5p	下游：GTGCAGGGTCCGAGGT
PYCR1	上游：GAAGATGGGGGTGAAGTTGA
PYCR1	下游：CTCAATGGAGCTGATGGTGA
GAPDH	上游：TCGGAGTCAACGGATTTGGT
GAPDH	下游：TTCCCGTTCTCAGCCTTGAC
U6	上游：GCTTCGGCAGCACATATA
U6	下游：AACGCTTCACGAATTTGCGT

组别	MIF-AS1	miR-423-5p	PYCR1
癌旁组织	1.00 ± 0.11	1.01 ± 0.12	1.02 ± 0.11
肿瘤组织	2.57 ± 0.28	0.32 ± 0.04	2.07 ± 0.22
t值	53.222	55.630	43.534
P值	< 0.001	< 0.001	< 0.001

组别	n	MIF-AS1	miR-423-5p	PYCR1
Control组	6	1.00 ± 0.10	1.00 ± 0.11	1.00 ± 0.12
si-NC组	6	1.02 ± 0.11	1.01 ± 0.12	1.02 ± 0.12
si-MIF-AS1组	6	0.43 ± 0.04^?#	1.86 ± 0.20^?#	0.30 ± 0.03^?#
si-MIF-AS1+anti-NC组	6	0.42 ± 0.04	1.88 ± 0.19	0.32 ± 0.03
si-MIF-AS1+anti-miR-423-5p组	6	0.44 ± 0.05	1.24 ± 0.12^&∧	0.86 ± 0.09^&∧
F值		109.014	49.980	101.240
P值		< 0.001	< 0.001	< 0.001

组别	细胞存活率（%）	细胞集落数（个）
Control组	100.14 ± 5.33	92.37 ± 8.55
si-NC组	99.87 ± 8.57	91.79 ± 9.31
si-MIF-AS1组	36.27 ± 4.62^?#	35.49 ± 5.20^?#
si-MIF-AS1+anti-NC组	37.03 ± 5.81	33.88 ± 4.74
si-MIF-AS1+anti-miR-423-5p组	74.36 ± 9.05^&∧	78.25 ± 7.34^&∧
F值	126.958	98.964
P值	< 0.001	< 0.001

组别	细胞迁移数目	细胞侵袭数目
Control组	187.65 ± 12.45	134.51 ± 10.87
si-NC组	185.36 ± 14.82	132.28 ± 11.16
si-MIF-AS1组	103.11 ± 11.48^?#	69.37 ± 8.60^?#
si-MIF-AS1+anti-NC组	101.59 ± 10.65	67.94 ± 10.05
si-MIF-AS1+anti-miR-423-5p组	162.89 ± 13.02^&∧	92.85 ± 7.66^&∧
F值	69.915	66.889
P值	< 0.001	< 0.001

Effect of lncRNA MIF⁃AS1 on the malignant biological behavior of prostate cancer cells by regulating the miR⁃423⁃5p/PYCR1 axis

RichHTML

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 11

References 26

Related Articles 15

Recommended Articles

Metrics

Comments

组别	细胞凋亡率（%）	PYCR1/ GAPDH
Control组	6.27 ± 0.80	0.88 ± 0.09
si-NC组	6.83 ± 0.91	0.86 ± 0.09
si-MIF-AS1组	29.43 ± 2.45^?#	0.25 ± 0.03^?#
si-MIF-AS1+anti-NC组	30.13 ± 3.70	0.27 ± 0.03
si-MIF-AS1+anti-miR-423-5p组	14.49 ± 1.73^&∧	0.73 ± 0.07^&∧
F值	171.043	129.131
P值	< 0.001	< 0.001

[1]	Weifeng LIU,Zheng DAI,Yibin ZHOU,Kaiwen FENG,Kai WEI,Gule SUN,Dongrong YANG,Jin. ZHU. The value of urine protein kinase Y⁃linked gene promoter site methylation in early diagnosis of prostate cancer [J]. The Journal of Practical Medicine, 2024, 40(5): 688-694.
[2]	Canwei CHEN,Zhuangwen LIAO,Ziwen FAN,Shuai HUANG,Yan HUANG,Binwei CHEN. LAMP3 inhibited the proliferation， metastatic and PC⁃3⁃induced vasculogenesis of HUVEC by regulating VEGF/AKT signaling [J]. The Journal of Practical Medicine, 2024, 40(2): 182-187.
[3]	Zhishi WANG,Guiling LI,Jingguo CHEN,Hong. WANG. Effects of miR⁃223 on prostate cancer cell damage by regulating Keap1/Nrf2/ARE signaling pathway [J]. The Journal of Practical Medicine, 2024, 40(17): 2375-2380.
[4]	DING Qi, SUN Mubin, JIN Xiaohua, FAN Zhijiang, TU Wenjian, LI Feng, SHI Yi, FAN Bo.. Efficacy and prognosis of cytoreductive radical prostatectomy combined with androgen deprivation therapy for oligometastatic prostate cancer [J]. The Journal of Practical Medicine, 2023, 39(4): 460-464.
[5]	Wenlu ZHANG,Chunyan. XU. Progress of SphK1/S1P in the biological behavior of tumor malignancy [J]. The Journal of Practical Medicine, 2023, 39(19): 2551-2555.
[6]	Minyu HUANG,Jun WU,Tianzi QIN,Wei ZHOU,Lize SU,Rong QIU,Lu. HUANG. The prognostic value of serum DCLK1 and sTim⁃3 in patients undergoing radical prostatectomy for prostate cancer [J]. The Journal of Practical Medicine, 2023, 39(18): 2368-2372.
[7]	ZHAO Haijun, LI Wei, WEI Yu, ZHANG Licui, ZHANG Yu, WANG Xinmin, WANG Cuizhe. . Effect of vitamin D on bone metastasis of prostate cancer mice induced by octanoic acid and high⁃fat diet [J]. The Journal of Practical Medicine, 2023, 39(14): 1756-1761.
[8]	HUANG Wei, FU Weijin, ZHANG Mingjin, YANG Xiaoli. . Research progress of pembrolizumab in the treatment of castration ⁃ resistant prostate cancer [J]. The Journal of Practical Medicine, 2023, 39(11): 1376-1382.
[9]	HUANG Shuai, HUANG Guoliang, LINGHU Xitao, XIE Shangyan, WA Qingde, GUO Yuanqing, HUANG Yan.. Study on the effect of betulinic acid on the biological behavior and osteoclast differentiation of PC⁃3 cells in acidic microenvironment [J]. The Journal of Practical Medicine, 2022, 38(9): 1076-1081.
[10]	CHEN Canwei, FAN Ziwen, HUANG Shuai, HUANG Yan, WA Qingde, LINGHU Xitao, LIAO Zhuangwen. . Effects of Diosmetin on proliferation，apoptosis，colony ⁃ formation，migration and cells adhesion of pros⁃ tate cancer PC⁃3 cells [J]. The Journal of Practical Medicine, 2022, 38(6): 721-725.
[11]	HUANG Sheng, GONG Rui, LIU Gangan, QI Qihua, HUANG Shuai. Effect of deoxyschizandrin on proliferation，migration and invasion of PC ⁃ 3 cells and its mechanism [J]. The Journal of Practical Medicine, 2021, 37(7): 851-857.
[12]	LIAO Zhuangwen, LIANG Caiyu, CHEN Canwei, YANG Jinshun, HUANG Shuai. Effect of Dictamnine on inhibition of PC ⁃ 3 cells with bone metastasis from prostate cancer via Wnt/beta ⁃catenin signaling pathway [J]. The Journal of Practical Medicine, 2021, 37(3): 298-303.
[13]	KONG Qi, WANG Zhanggui.. Progress in the treatment of advanced prostate cancer [J]. The Journal of Practical Medicine, 2021, 37(3): 410-414.
[14]	XIE Shangyan, HUANG Shuai, WANG Bin, LIN Zhuoyuan, ZHONG Shaowen, LIANG Baoxia.. Effects of Betulinic acid on stemness，invasion，migration，adhesion and HIF⁃1α expression in PC⁃3 cells under hypoxia [J]. The Journal of Practical Medicine, 2021, 37(24): 3119-3125.
[15]	ZHOU Lin, WANG Zhengfang, YU Junjie, WU Yinxia, HAN Chongxu, WANG Guangzhou. . Clinical study of bone turnover markers and prediction model constructed by bone turnover markers，IL⁃6， and tPSA in prostate cancer bone metastasis [J]. The Journal of Practical Medicine, 2021, 37(24): 3197-3201.