Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Aug;52(2):68.
doi: 10.3892/ijmm.2023.5271. Epub 2023 Jun 23.

Long non‑coding RNAs as potential therapeutic targets in non‑small cell lung cancer (Review)

Peiyu Tang  1 , Dejuan Sun  1 , Wei Xu  2 , Hua Li  1 , Lixia Chen  1
Affiliations
Review

Long non‑coding RNAs as potential therapeutic targets in non‑small cell lung cancer (Review)

Peiyu Tang et al. Int J Mol Med. 2023 Aug.

Abstract

Non‑small cell lung cancer (NSCLC) is one of the most common malignancies with a high morbidity and mortality rate. Long non‑coding RNAs (lncRNAs) have been reported to be closely associated with the occurrence and progression of NSCLC. In addition, lncRNAs have been documented to participate in the development of drug resistance and radiation sensitivity in patients with NSCLC. Due to their extensive functional characterization, high tissue specificity and sex specificity, lncRNAs have been proposed to be novel biomarkers and therapeutic targets for NSCLC. Therefore, in the current review, the functional classification of lncRNAs were presented, whilst the potential roles of lncRNAs in NSCLC were also summarized. Various physiological aspects, including proliferation, invasion and drug resistance, were all discussed. It is anticipated that the present review will provide a perspective on lncRNAs as potential diagnostic molecular biomarkers and therapeutic targets for NSCLC.

Keywords: NSCLC; biomarkers; drug resistance; lncRNA; therapeutic targets.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Mechanisms of lncRNAs in nucleus and cytoplasm. In the nucleus, ① lncRNAs regulate chromatin or act as scaffolds to recruit multiple regulatory molecules to gene promoters to activate or suppress gene expression, ② regulate messenger RNA processing by recruiting regulatory molecules to messenger RNA, ③ and bind to numerous chromatin remodelers and regulated histones, thereby promoting or suppressing gene expression, or modifying DNA to suppress gene expression. In cytoplasm, ④ lncRNAs regulate mRNA stability by directly binding to mRNA to form RNA-RNA duplexes, ⑤ interact with proteins to regulate signaling cascades and subsequent changes in gene expression, ⑥ and act as miRNA sponges to competitively bind miRNA regulation, which in turn has an impact on ⑦ signaling pathways. lncRNA, long non-coding RNA; miR, microRNA.
Figure 2
Figure 2
Mechanisms of lncRNAs regulating the proliferation and apoptosis of NSCLC. (A) PIK3CD-AS2 inhibits p53 signaling by binding with p53 negative regulator YBX1. (B) MALAT1 inhibits p53 signaling by upregulating miR-185-5p and reducing the expression of MDM4. (C) UPLA1 facilitates Wnt/β-catenin signaling by binding to DSP. (D) XIST modulates miR-744 by serving as an endogenous competitive RNA, increasing RING1 expression and enhancing the Wnt/β-catenin signaling pathway. (E) SLC16A1-AS1 affects overall survival and progression-free survival in NSCLC by regulating the RAS/RAF/MEK/ERK signaling pathway. lncRNA, long non-coding RNA; NSCLC, non-small cell lung cancer; PIK3CD-AS2, PIK3CD antisense RNA 2; YBX1, Y-box binding protein 1; MALAT1, metastasis-associated lung adenocarcinoma transcript 1; MDM4, murine double minute 4; UPLA1, lung adenocarcinoma related transcriptional-1; DSP, desmoplakin; XIST, candidate gene for X-inactivation center; miR, microRNA; RING1, really interesting new gene 1; lncRNA SLC16A1-AS1, SLC16A1 antisense transcript 1.
Figure 3
Figure 3
Mechanisms of CASC9 and lncRNA UCA1 in drug resistance in NSCLC. (A) CASC9 suppresses the tumor suppressor DUSP1 by recruiting histone methyltransferase EZH2 and increasing the resistance to gefitinib. (B) LncRNA UCA1 acts as an endogenous competitive RNA that can bind with miR-143 to regulate the expression of FOSL2. In addition, lncRNA UCA1 increases resistance to cisplatin through the UCA1/miR-495/NRF2 signaling pathway. CASC9, candidate tumor susceptibility gene 9; lncRNA, long non-coding RNA; UCA1, lncRNA urothelial carcinoma-associated; NSCLC, non-small cell lung cancer; DUSP1, dual specificity phosphatase 1; miR, microRNA; EZH2, zeste homolog 2.
Figure 4
Figure 4
Mechanisms of KCNQ1OT1 and linc-spry3-2/3/4 in radio-sensitivity in NSCLC. (A) KCNQ1OT1 antagonizes SBRT by inducing ATG5 and ATG12-dependent autophagy by sponging miR-372-3p. (B) The binding of linc-spry3-2/3/4 to IGF2BP3 affects the half-life of certain mRNAs, including the anti-apoptotic HMGA2 mRNA and the oncogenic c-Myc mRNA. KCNQ1OT1, opposite strand/antisense transcript 1; NSCLC, non-small cell lung cancer; SBRT, stereotactic radiotherapy; ATG, autophagy-related; miR, microRNA; HMGA2, high mobility group AT-Hook 2.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality Worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–249. doi: 10.3322/caac.21660. - DOI - PubMed
    1. Xie S, Wu Z, Qi Y, Wu B, Zhu X. The metastasizing mechanisms of lung cancer: Recent advances and therapeutic challenges. Biomed Pharmacother. 2021;138:111450. doi: 10.1016/j.biopha.2021.111450. - DOI - PubMed
    1. Campbell JD, Alexandrov A, Kim J, Wala J, Berger AH, Pedamallu CS, Shukla SA, Guo G, Brooks AN, Murray BA, et al. Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas. Nat Genet. 2016;48:607–616. doi: 10.1038/ng.3564. - DOI - PMC - PubMed
    1. Chaft JE, Rimner A, Weder W, Azzoli CG, Kris MG, Cascone T. Evolution of systemic therapy for stages I-III non-metastatic non-small-cell lung cancer. Nat Rev Clin Oncol. 2021;18:547–557. doi: 10.1038/s41571-021-00501-4. - DOI - PMC - PubMed
    1. Howlader N, Forjaz G, Mooradian MJ, Meza R, Kong CY, Cronin KA, Mariotto AB, Lowy DR, Feuer EJ. The effect of advances in lung-cancer treatment on population mortality. N Engl J Med. 2020;383:640–649. doi: 10.1056/NEJMoa1916623. - DOI - PMC - PubMed

MeSH terms

Grants and funding

The present study was supported by the National Natural Science Foundation of China (NSFC) (grant no. 82204224), the Chunhui Program-Cooperative Research Project of the Ministry of Education, Liaoning Natural Science Foundation (grant no. 2022-MS-241), the China Postdoctoral Science Foundation (grant no. 2021M693957), the Shenyang Young and Middle-aged Innovative Talents Support Program (grant no. RC210446), and the Project of the Educational Department of Liaoning (grant no. LJKZ0919).