LncRNAs As Theragnostic Biomarkers for Predicting Radioresistance in Cancer: A Systematic Review and Meta-Analysis

Overview

Journal Front Oncol

Specialty Oncology

Date 2022 Jun 13

PMID 35692742

Authors

Ping Lin

Wenmin Xing

Qian Ren

Qin Wang

Jing Yan

Genxiang Mao

Affiliations

Soon will be listed here.

Abstract

Background: Radioresistance is the major obstacle after cancer radiotherapy. The dysregulation of long non-coding RNAs (lncRNAs) was closely related the radioresistance response. This meta-analysis was aimed to interpret the relationship between lncRNAs and radiotherapy responses in different cancers.

Method: The studies were selected from databases including PubMed, ISI Web of Science, Embase, Google Scholar, PMC, and CNKI (China National Knowledge Infrastructure). The publication time was limited to before March 20, 2021. The hazard ratios (HRs) and 95% confidence interval were calculated with random-effects models. Subgroup analyses, sensitivity analyses, and publication bias were also conducted.

Result: Twenty-seven lncRNAs in 14 cancer types were investigated, in which 23 lncRNAs were upregulated and four lncRNAs were downregulated. Dysregulation of these lncRNAs were found to be related to radioresistance response. The pooled HR and 95% confidence interval for the combined up-regulated lncRNAs was 1.73 (95% CI=1.50-2.00; P< 0.01) and down-regulated lncRNAs was 2.09 (95% CI= 1.60-2.72; P< 0.01). The HR values of the subgroup analysis for glioma (HR= 2.22, 95% CI= 1.79-2.74; p< 0.01), non-small cell lung cancer (HR=1.48, 95% CI=1.18-1.85; P<0.01), nasopharyngeal carcinoma (HR=4.26; 95% CI= 1.58-11.46; P< 0.01), and breast cancer (HR=1.29; 95% CI= 1.08-1.54; P< 0.01) were obtained. Moreover, the expression of lncRNAs was significantly related to overall survival of patients no matter if the sample size was >50 or not. In addition, the HR values of the subgroup analysis for lncRNA H19 (HR=2.68; 95% CI= 1.92-3.74; P <0.01), lncRNA FAM201A (HR=2.15; 95% CI= 1.15-3.99; P <0.01), and lncRNA HOTAIR (HR=1.22; 95% CI= 0.98-1.54; P =0.08) were also obtained.

Conclusion: LncRNAs can induce cancer radioresistance by regulating cell death-related signaling pathways. Results indicated that lncRNAs, especially lncRNA H19, FAM201A, and HOTAIR, could be considered as a predictive theragnostic biomarker to evaluate radiotherapy response.

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References

Chen L, Yuan D, Yang Y, Ren M . LincRNA-p21 enhances the sensitivity of radiotherapy for gastric cancer by targeting the β-catenin signaling pathway. J Cell Biochem. 2018; 120(4):6178-6187. DOI: 10.1002/jcb.27905. View

Zhang J, Li W . Long noncoding RNA CYTOR sponges miR-195 to modulate proliferation, migration, invasion and radiosensitivity in nonsmall cell lung cancer cells. Biosci Rep. 2018; 38(6). PMC: 6435535. DOI: 10.1042/BSR20181599. View

Jing L, Yuan W, Ruofan D, Jinjin Y, Haifeng Q . HOTAIR enhanced aggressive biological behaviors and induced radio-resistance via inhibiting p21 in cervical cancer. Tumour Biol. 2014; 36(5):3611-9. DOI: 10.1007/s13277-014-2998-2. View

Stang A . Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010; 25(9):603-5. DOI: 10.1007/s10654-010-9491-z. View

Li J, Lei C, Chen B, Zhu Q . LncRNA FGD5-AS1 Facilitates the Radioresistance of Breast Cancer Cells by Enhancing MACC1 Expression Through Competitively Sponging miR-497-5p. Front Oncol. 2021; 11:671853. PMC: 8250440. DOI: 10.3389/fonc.2021.671853. View

Liu Y, Yue P, Zhou T, Zhang F, Wang H, Chen X . LncRNA MEG3 enhances I sensitivity in thyroid carcinoma via sponging miR-182. Biomed Pharmacother. 2018; 105:1232-1239. DOI: 10.1016/j.biopha.2018.06.087. View

Zhang S, Wang B, Xiao H, Dong J, Li Y, Zhu C . LncRNA HOTAIR enhances breast cancer radioresistance through facilitating HSPA1A expression via sequestering miR-449b-5p. Thorac Cancer. 2020; 11(7):1801-1816. PMC: 7327697. DOI: 10.1111/1759-7714.13450. View

Zhang M, Gao C, Yang Y, Li G, Dong J, Ai Y . Long Noncoding RNA CRNDE/PRC2 Participated in the Radiotherapy Resistance of Human Lung Adenocarcinoma Through Targeting p21 Expression. Oncol Res. 2017; 26(8):1245-1255. PMC: 7844700. DOI: 10.3727/096504017X14944585873668. View

Liu Y, Chen X, Chen X, Liu J, Gu H, Fan R . Long non-coding RNA HOTAIR knockdown enhances radiosensitivity through regulating microRNA-93/ATG12 axis in colorectal cancer. Cell Death Dis. 2020; 11(3):175. PMC: 7060216. DOI: 10.1038/s41419-020-2268-8. View

10.

Cheng W, Shi X, Lin M, Yao Q, Ma J, Li J . LncRNA MAGI2-AS3 Overexpression Sensitizes Esophageal Cancer Cells to Irradiation Through Down-Regulation of HOXB7 EZH2. Front Cell Dev Biol. 2020; 8:552822. PMC: 7732634. DOI: 10.3389/fcell.2020.552822. View

11.

Bi Z, Li Q, Dinglin X, Xu Y, You K, Hong H . Nanoparticles (NPs)-Meditated LncRNA AFAP1-AS1 Silencing to Block Wnt/-Catenin Signaling Pathway for Synergistic Reversal of Radioresistance and Effective Cancer Radiotherapy. Adv Sci (Weinh). 2020; 7(18):2000915. PMC: 7509644. DOI: 10.1002/advs.202000915. View

12.

Sahu A, Singhal U, Chinnaiyan A . Long noncoding RNAs in cancer: from function to translation. Trends Cancer. 2015; 1(2):93-109. PMC: 4672369. DOI: 10.1016/j.trecan.2015.08.010. View

13.

Jin C, Yan B, Lu Q, Lin Y, Ma L . The role of MALAT1/miR-1/slug axis on radioresistance in nasopharyngeal carcinoma. Tumour Biol. 2015; 37(3):4025-33. DOI: 10.1007/s13277-015-4227-z. View

14.

Schaue D, McBride W . Opportunities and challenges of radiotherapy for treating cancer. Nat Rev Clin Oncol. 2015; 12(9):527-40. PMC: 8396062. DOI: 10.1038/nrclinonc.2015.120. View

15.

Tang G, Luo L, Zhang J, Zhai D, Huang D, Yin J . lncRNA LINC01057 promotes mesenchymal differentiation by activating NF-κB signaling in glioblastoma. Cancer Lett. 2020; 498:152-164. DOI: 10.1016/j.canlet.2020.10.047. View

16.

Wang M, Wang L, He X, Zhang J, Zhu Z, Zhang M . lncRNA CCAT2 promotes radiotherapy resistance for human esophageal carcinoma cells via the miR‑145/p70S6K1 and p53 pathway. Int J Oncol. 2019; 56(1):327-336. DOI: 10.3892/ijo.2019.4929. View

17.

Chin C, Chen S, Wu H, Ho C, Ko M, Lin C . cytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Syst Biol. 2014; 8 Suppl 4:S11. PMC: 4290687. DOI: 10.1186/1752-0509-8-S4-S11. View

18.

Boileve A, Hilmi M, Delaye M, Tijeras-Raballand A, Neuzillet C . Biomarkers in Hepatobiliary Cancers: What is Useful in Clinical Practice?. Cancers (Basel). 2021; 13(11). PMC: 8198554. DOI: 10.3390/cancers13112708. View

19.

Podralska M, Ciesielska S, Kluiver J, van den Berg A, Dzikiewicz-Krawczyk A, Slezak-Prochazka I . Non-Coding RNAs in Cancer Radiosensitivity: MicroRNAs and lncRNAs as Regulators of Radiation-Induced Signaling Pathways. Cancers (Basel). 2020; 12(6). PMC: 7352793. DOI: 10.3390/cancers12061662. View

20.

Li J, Liu X, Nan S, Xu C . Silencing of long non-coding RNA LINC00520 promotes radiosensitivity of head and neck squamous cell carcinoma cells. Free Radic Res. 2020; 54(4):254-270. DOI: 10.1080/10715762.2020.1752373. View