LncRNA RP3-326I13.1 promotes cisplatin resistance in lung adenocarcinoma by binding to HSP90B and upregulating MMP13

被引：13

作者：

Zhou, Huixin ^{[1
]}

Huang, Xiaolu ^{[1
]}

Shi, Wenjing ^{[1
]}

Xu, Shihao ^{[2
]}

Chen, Jie ^{[3
]}

Huang, Kate ^{[4
]}

Wang, Yumin ^{[1
]}

机构：

[1] Wenzhou Med Univ, Dept Lab Med, Affiliated Hosp 1, Nanbaixiang St, Wenzhou 325000, Peoples R China

[2] Wenzhou Med Univ, Dept Ultrasound Imaging, Affiliated Hosp 1, Wenzhou, Peoples R China

[3] Wenzhou Med Univ, Dept Intens Care Unit, Affiliated Hosp 1, Wenzhou, Peoples R China

[4] Wenzhou Med Univ, Dept Pathol, Affiliated Hosp 1, Nanbaixiang St, Wenzhou 325000, Peoples R China

来源：

CELL CYCLE | 2022年 / 21卷 / 13期

基金：

中国国家自然科学基金;

关键词：

Lung adenocarcinoma; cisplatin resistance; 1; CHEMOTHERAPY; MECHANISMS; PROTEINS; GENES;

D O I：

10.1080/15384101.2022.2051971

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Cisplatin (DDP) resistance has become the major obstacle in the therapy of malignant tumors, including lung adenocarcinoma (LAD). Long non-coding RNAs (lncRNAs) were confirmed to be related to DDP-resistance. Studies have shown that RP3-326I13.1 (also known as PINCR) could promote the progression of colorectal cancer, and RP3-326I13.1 knockdown could induce hypersensitivity to chemotherapy drugs. While the function of RP3-326I13.1 in LAD is unclear, therefore, this study aimed to research the biological function and related molecular mechanisms of RP3-326I13.1 in DDP-resistance of LAD. QPCR analysis found that RP3-326I13.1 was highly expressed in A549/DDP cells and LAD tissues. Cytological assays found that RP3-326I13.1 pro-moted the proliferation, migration, invasion, and DDP-resistance of LAD cell lines. Moreover, knock-down of RP3-326I13.1 could induce G1 phase arrest. Nude mouse xenograft assay confirmed that RP3-326I13.1 could promote tumor growth and DDP-resistance in vivo. Mechanically, RNA pull-down and mass spectrometry analysis indicated that heat shock protein HSP 90-beta (HSP90B) could be combined with RP3-326I13.1. HSP90B knockdown inhibited the effect of RP3-326I13.1 on proliferation, invasion, and promoted LAD cell lines apoptosis. Transcriptome sequencing analysis found that MMP13 was the downstream mRNA of RP3-326I13.1. In conclusion, RP3-326I13.1 could promote DDP-resistance of LAD by binding to HSP90B and upregulating human matrix metalloproteinase-13 (MMP-13) and may serve as a therapeutic target, as well as a biomarker for predicting DDP-resistance in LAD. Abbreviations: DDP: Cisplatin; LAD: Lung adenocarcinoma; LncRNAs: Long non-coding RNAs; qPCR: real-time fluorescent quantitative PCR; HSP90B: Heat shock protein HSP 90-beta; RPMI: Roswell Park Memorial Institute; FBS: Fetal bovine serum; CT: computed tomography; MRI: magnetic resonance imaging; RECIST: Response evaluation criteria in solid tumors; NC: Negative control; OE: overexpression; shRNA: short hairpin RNA; siRNA: small interfering RNA; CCK-8: Cell Counting Kit-8; IC50: The half maximal inhibitory concentration; PBS: Phosphate buffer saline; PI: propidium iodide; SDS-PAGE: sodiumdodecylsulfate-polyacrylamide gel electrophoresis; ceRNA: Competing endogenous RNA; HE: hematoxylin-eosin; ns: no significance.

引用

页码：1391 / 1405

页数：15

共 38 条

[1] World Medical Association Declaration of Helsinki Ethical Principles for Medical Research Involving Human Subjects [J].

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2013, 310 (20) :2191-2194

[2] Matrix metalloproteinase-7 and -13 expression associate to cisplatin resistance in head and neck cancer cell lines [J].

Ansell, Anna ;

Jerhammar, Fredrik ;

Ceder, Rebecca ;

Grafstrom, Roland ;

Grenman, Reidar ;

Roberg, Karin .

ORAL ONCOLOGY, 2009, 45 (10) :866-871

[3] Adjuvant chemotherapy, with or without postoperative radiotherapy, in operable non-small-cell lung cancer: two meta-analyses of individual patient data [J].

Auperin, A. ;

Le Chevalier, T. ;

Le Pechoux, C. ;

Pignon, J. P. ;

Tribodet, H. ;

Burdett, S. ;

Stewart, L. A. ;

Tierney, J. F. ;

Stephens, R. J. ;

Arriagada, R. ;

Higgins, J. P. ;

Johnson, D. H. ;

van Meerbeeck, J. ;

Parmar, M. K. B. ;

Souhami, R. L. ;

Bergman, B. ;

Dautzenberg, B. ;

Douillard, J. Y. ;

Dunant, A. ;

Endo, C. ;

Girling, D. J. ;

Imaizumi, M. ;

Kato, H. ;

Keller, S. M. ;

Kimura, H. ;

Knuuttila, A. ;

Kodama, K. ;

Komaki, R. ;

Kris, M. G. ;

Lad, T. ;

Mineo, T. ;

Park, J. H. ;

Piantadosi, S. ;

Pyrhonen, S. ;

Rosell, R. ;

Scagliotti, G. V. ;

Seymour, L. W. ;

Shepherd, F. A. ;

Spiro, S. G. ;

Strauss, G. M. ;

Sylvester, R. ;

Tada, H. ;

Tanaka, F. ;

Torri, V. ;

Wada, H. ;

Waller, D. ;

Xu, G. C. .

LANCET, 2010, 375 (9722) :1267-1277

[4] Targeting Heat Shock Proteins in Cancer: A Promising Therapeutic Approach [J].

Chatterjee, Suman ;

Burns, Timothy F. .

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2017, 18 (09)

[5] Prosurvival long noncoding RNA PINCR regulates a subset of p53 targets in human colorectal cancer cells by binding to Matrin 3 [J].

Chaudhary, Ritu ;

Gryder, Berkley ;

Woods, Wendy S. ;

Subramanian, Murugan ;

Jones, Matthew F. ;

Li, Xiao Ling ;

Jenkins, Lisa M. ;

Shabalina, Svetlana A. ;

Mo, Min ;

Dasso, Mary ;

Yang, Yuan ;

Wakefield, Lalage M. ;

Zhu, Yuelin ;

Friers, Susan M. ;

Moriarityl, Branden S. ;

Prasanth, Kannanganattu V. ;

Perez-Pinera, Pablo ;

Lal, Ashish .

ELIFE, 2017, 6

[6] The HSP90 family of genes in the human genome: Insights into their divergence and evolution [J].

Chen, B ;

Piel, WH ;

Gui, LM ;

Bruford, E ;

Monteiro, A .

GENOMICS, 2005, 86 (06) :627-637

[7] New Insights into Mechanisms of Cisplatin Resistance: From Tumor Cell to Microenvironment [J].

Chen, Shang-Hung ;

Chang, Jang-Yang .

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2019, 20 (17)

[8] Roles of Long Noncoding RNAs in Recurrence and Metastasis of Radiotherapy-Resistant Cancer Stem Cells [J].

Chi, Hsiang-Cheng ;

Tsai, Chung-Ying ;

Tsai, Ming-Ming ;

Yeh, Chau-Ting ;

Lin, Kwang-Huei .

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2017, 18 (09)

[9] Reporting animal research: Explanation and elaboration for the ARRIVE guidelines 2.0 [J].

du Sert, Nathalie Percie ;

Ahluwalia, Amrita ;

Alam, Sabina ;

Avey, Marc T. ;

Baker, Monya ;

Browne, William J. ;

Clark, Alejandra ;

Cuthill, Innes C. ;

Dirnagl, Ulrich ;

Emerson, Michael ;

Garner, Paul ;

Holgate, Stephen T. ;

Howells, David W. ;

Hurst, Viki ;

Karp, Natasha A. ;

Lazic, Stanley E. ;

Lidster, Katie ;

MacCallum, Catriona J. ;

Macleod, Malcolm ;

Pearl, Esther J. ;

Petersen, Ole H. ;

Rawle, Frances ;

Reynolds, Penny ;

Rooney, Kieron ;

Sena, Emily S. ;

Silberberg, Shai D. ;

Steckler, Thomas ;

Wuerbel, Hanno .

PLOS BIOLOGY, 2020, 18 (07)

[10] Mechanisms of cell uptake and toxicity of the anticancer drug cisplatin [J].

Eljack, Nasma D. ;

Ma, Ho-Yu M. ;

Drucker, Janine ;

Shen, Clara ;

Hambley, Trevor W. ;

New, Elizabeth J. ;

Friedrich, Thomas ;

Clarke, Ronald J. .

METALLOMICS, 2014, 6 (11) :2126-2133

← 1 2 3 4 →