Effects of lncRNA PKD2-2-3 on cell proliferation, clone formation, migration, and invasion of lung adenocarcinoma

doi:10.19401/j.cnki.1007-3639.2023.08.001

Abstract

Abstract:

Background and purpose: Long non-coding RNA (lncRNA) is abnormally expressed in lung adenocarcinoma patients, and closely related to tumor occurrence, development and chemotherapy resistance. In this study, we mainly investigated the biological function of lncRNA PKD2-2-3 and verified its effect on the proliferation, colony formation, migration and invasion in lung adenocarcinoma. Methods: Three pairs of lung adenocarcinoma tissues and adjacent tissues were analyzed based on expression profiling Affymetrix® GeneChip Human Transcriptome Array 2.0 (HTA2.0), and we focused on lncRNA PKD2-2-3 that showed most significant difference between lung adenocarcinoma issues and adjacent tissues. Besides, we found the upregulated expression of lncRNA PKD2-2-3 in lung adenocarcinoma tissues and suggested the relation of lncRNA PKD2-2-3 expression with prognosis by using GSE19188 and GSE30219 data in Gene Expression Omnibus (GEO) database. Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) was used to detect the expression of lncRNA PKD2-2-3 in cell lines including HBE, A549 and PC9. After using siRNAs to decrease the expression of lncRNA PKD2-2-3 in A549 and PC9, we detected cell proliferation and colony formation by cell counting kit-8 (CCK-8) assay and colony formation assay. Effects of lncRNA PKD2-2-3 on migration and invasion in lung adenocarcinoma cells were detected by wound-healing assay and transwell assay, respectively. Moreover, we detected expression levels of E-cadherin and N-cadherin that were epithelial-mesenchymal transition (EMT) related genes by Western blot. The effect of lncRNA PKD2-2-3 on the formation and growth of lung adenocarcinoma in vivo was verified by subcutaneous transplantation tumor model. Results: LncRNA PKD2-2-3 was highly expressed in lung adenocarcinoma tissue, and was positively associated with poor prognosis of lung adenocarcinoma patients. Compared with human bronchial epithelial cells (HBE), lncRNA PKD2-2-3 was overexpressed in A549 and PC9. The proliferation, colony formation, migration and invasion of lung adenocarcinoma cells were significantly inhibited when decreasing the expression level of lncRNA PKD2-2-3. Western blot also showed that the expression level of E-cadherin was increased, while the level of N-cadherin was decreased after lncRNA PKD2-2-3 knockdown. Subcutaneous tumor transplantation experiments showed that lncRNA PKD2-2-3 knockdown inhibited the growth of lung adenocarcinoma in vivo. Conclusion: LncRNA PKD2-2-3 expression was upregulated in lung adenocarcinoma tissues, and it was associated with poor prognosis of lung adenocarcinoma patients. Overexpression of lncRNA PKD2-2-3 promoted the proliferation, colony formation, migration and invasion of lung adenocarcinoma cells. LncRNA PKD2-2-3 level was closely related to EMT process in lung adenocarcinoma in vitro and in vivo.

Key words: Lung adenocarcinoma, LncRNA PKD2-2-3, Cell migration, Cell invasion, Epithelial-mesenchymal transition

CLC Number:

R734.2

JIA Liqing, GE Xiaolu, JIANG Lin, ZHOU Xiaoyan. Effects of lncRNA PKD2-2-3 on cell proliferation, clone formation, migration, and invasion of lung adenocarcinoma[J]. China Oncology, 2023, 33(8): 717-725.

Figures/Tables 4

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References 16

[1]	SIEGEL R, MA J M, ZOU Z H, et al. Cancer statistics, 2023[J]. CA A Cancer J Clin, 2023, 73(1): 17-48. doi: 10.3322/caac.v73.1
[2]	CHEN P X, LIU Y H, WEN Y K, et al. Non-small cell lung cancer in China[J]. Cancer Commun (Lond), 2022, 42(10): 937-970.
[3]	CHI Y J, WANG D, WANG J P, et al. Long non-coding RNA in the pathogenesis of cancers[J]. Cells, 2019, 8(9): 1015. doi: 10.3390/cells8091015
[4]	GE X L, LI G Y, JIANG L, et al. Long non-coding RNA CAR10 promotes lung adenocarcinoma metastasis via miR-203/30/SNAI axis[J]. Oncogene, 2019, 38(16): 3061-3076. doi: 10.1038/s41388-018-0645-x
[5]	JIANG M, QI F, ZHANG K, et al. MARCKSL1-2 reverses docetaxel-resistance of lung adenocarcinoma cells by recruiting SUZ12 to suppress HDAC1 and elevate miR-200b[J]. Mol Cancer, 2022, 21(1): 150. doi: 10.1186/s12943-022-01605-w pmid: 35864549
[6]	ZHANG L, MA D L, LI F J, et al. Lnc-PKD2-2-3/miR-328/GPAM ceRNA network induces cholangiocarcinoma proliferation, invasion and 5-FU chemoresistance[J]. Front Oncol, 2022, 12: 871281. doi: 10.3389/fonc.2022.871281
[7]	QIU G C, MA D L, LI F J, et al. Lnc-PKD2-2-3, identified by long non-coding RNA expression profiling, is associated with pejorative tumor features and poor prognosis, enhances cancer stemness and may serve as cancer stem-cell marker in cholangiocarcinoma[J]. Int J Oncol, 2019, 55(1): 45-58. doi: 10.3892/ijo.2019.4798 pmid: 31059014
[8]	JIA L Q, GE X L, DU C, et al. EEF1A2 interacts with HSP90AB1 to promote lung adenocarcinoma metastasis via enhancing TGF-β/SMAD signalling[J]. Br J Cancer, 2021, 124(7): 1301-1311. doi: 10.1038/s41416-020-01250-4
[9]	HOU J, AERTS J, DEN HAMER B, et al. Gene expression-based classification of non-small cell lung carcinomas and survival prediction[J]. PLoS One, 2010, 5(4): e10312.
[10]	ROUSSEAUX S, DEBERNARDI A, JACQUIAU B, et al. Ectopic activation of germline and placental genes identifies aggressive metastasis-prone lung cancers[J]. Sci Transl Med, 2013, 5(186): 186ra66.
[11]	LI T F, ZHOU S, YANG Y, et al. LncRNA MNX1-AS1: a novel oncogenic propellant in cancers[J]. Biomedecine Pharmacother, 2022, 149: 112801.
[12]	FARZANEH M, GHASEMIAN M, GHAEDRAHMATI F, et al. Functional roles of lncRNA-TUG1 in hepatocellular carcinoma[J]. Life Sci, 2022, 308: 120974. doi: 10.1016/j.lfs.2022.120974
[13]	FARZANEH M, NAJAFI S, ANBIYAEE O, et al. LncRNA MALAT1-related signaling pathways in osteosarcoma[J]. Clin Transl Oncol, 2023, 25(1): 21-32. doi: 10.1007/s12094-022-02876-x
[14]	ZHANG Y X, YUAN J, GAO Z M, et al. LncRNA TUC338 promotes invasion of lung cancer by activating MAPK pathway[J]. Eur Rev Med Pharmacol Sci, 2018, 22(2): 443-449.
[15]	TIAN H, LIAN R, LI Y, et al. AKT-induced lncRNA VAL promotes EMT-independent metastasis through diminishing Trim16-dependent vimentin degradation[J]. Nat Commun, 2020, 11(1): 5127. doi: 10.1038/s41467-020-18929-0 pmid: 33046716
[16]	HASHEMI M, MOOSAVI M S, ABED H M, et al. Long non-coding RNA (lncRNA) H19 in human cancer: from proliferation and metastasis to therapy[J]. Pharmacol Res, 2022, 184: 106418. doi: 10.1016/j.phrs.2022.106418