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
. 2024 Jun 18;25(12):6685.
doi: 10.3390/ijms25126685.

MiRNAs and Microbiota in Non-Small Cell Lung Cancer (NSCLC): Implications in Pathogenesis and Potential Role in Predicting Response to ICI Treatment

Francesco Nucera  1 , Paolo Ruggeri  1 , Calogera Claudia Spagnolo  2 , Mariacarmela Santarpia  2 , Antonio Ieni  3 , Francesco Monaco  4 , Giovanni Tuccari  3 , Giovanni Pioggia  5 , Sebastiano Gangemi  6
Affiliations
Review

MiRNAs and Microbiota in Non-Small Cell Lung Cancer (NSCLC): Implications in Pathogenesis and Potential Role in Predicting Response to ICI Treatment

Francesco Nucera et al. Int J Mol Sci. .

Abstract

Lung cancer (LC) is one of the most prevalent cancers in both men and women and today is still characterized by high mortality and lethality. Several biomarkers have been identified for evaluating the prognosis of non-small cell lung cancer (NSCLC) patients and selecting the most effective therapeutic strategy for these patients. The introduction of innovative targeted therapies and immunotherapy with immune checkpoint inhibitors (ICIs) for the treatment of NSCLC both in advanced stages and, more recently, also in early stages, has revolutionized and significantly improved the therapeutic scenario for these patients. Promising evidence has also been shown by analyzing both micro-RNAs (miRNAs) and the lung/gut microbiota. MiRNAs belong to the large family of non-coding RNAs and play a role in the modulation of several key mechanisms in cells such as proliferation, differentiation, inflammation, and apoptosis. On the other hand, the microbiota (a group of several microorganisms found in human orgasms such as the gut and lungs and mainly composed by bacteria) plays a key role in the modulation of inflammation and, in particular, in the immune response. Some data have shown that the microbiota and the related microbiome can modulate miRNAs expression and vice versa by regulating several intracellular signaling pathways that are known to play a role in the pathogenesis of lung cancer. This evidence suggests that this axis is key to predicting the prognosis and effectiveness of ICIs in NSCLC treatment and could represent a new target in the treatment of NSCLC. In this review, we highlight the most recent evidence and data regarding the role of both miRNAs and the lung/gut microbiome in the prediction of prognosis and response to ICI treatment, focusing on the link between miRNAs and the microbiome. A new potential interaction based on the underlying modulated intracellular signaling pathways is also shown.

Keywords: ICI treatment; NSCLC; biomarkers; lung/gut microbiota; miRNAs.

PubMed Disclaimer

Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Known and potential interactions between miRNAs and microbiota modulating both prognosis and ICI treatment response in NSCLC. MiRNA/microbiota interactions modulating the prognosis in patients with NSCLC are shown on the left. miRNA/microbiota interactions modulating ICI treatment response in NSCLC are shown on the right. The interactions marked in black are already well known. The interactions marked in red are potential interactions that have been found in other cancers and that can modulate the same signaling pathways involved in NSCLC. The interactions marked in blue are well-known interactions that have been found in other chronic inflammatory diseases. Legend: +—increased expression, -—decreased expression; ?—unknown.
Figure 2
Figure 2
Modulation of key intracellular signaling pathways involved in lung cancer development mediated by the interaction between microbiota and miRNAs. There is an interaction between gut/lung microbiota and miRNA expression. Microbiota dysbiosis can alter the expression of several miRNAs, and vice versa. Both microbiota and the related microbiome and miRNAs play a crucial role in the modulation of key intracellular signaling pathways involved in lung cancer development. Some of these interactions may be correlated to poor patient prognosis with fewer benefits from the treatment and consequently lower survival rates.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Kielbowski K., Ptaszynski K., Wojcik J., Wojtys M.E. The role of selected non-coding RNAs in the biology of non-small cell lung cancer. Adv. Med. Sci. 2023;68:121–137. doi: 10.1016/j.advms.2023.02.004. - DOI - PubMed
    1. Goh K.Y., Cheng T.Y., Tham S.C., Lim D.W. Circulating Biomarkers for Prediction of Immunotherapy Response in NSCLC. Biomedicines. 2023;11:508. doi: 10.3390/biomedicines11020508. - DOI - PMC - PubMed
    1. Indini A., Rijavec E., Grossi F. Circulating Biomarkers of Response and Toxicity of Immunotherapy in Advanced Non-Small Cell Lung Cancer (NSCLC): A Comprehensive Review. Cancers. 2021;13:1794. doi: 10.3390/cancers13081794. - DOI - PMC - PubMed
    1. Boeri M., Milione M., Proto C., Signorelli D., Lo Russo G., Galeone C., Verri C., Mensah M., Centonze G., Martinetti A., et al. Circulating miRNAs and PD-L1 Tumor Expression Are Associated with Survival in Advanced NSCLC Patients Treated with Immunotherapy: A Prospective Study. Clin. Cancer Res. 2019;25:2166–2173. doi: 10.1158/1078-0432.CCR-18-1981. - DOI - PMC - PubMed
    1. Fan J., Yin Z., Xu J., Wu F., Huang Q., Yang L., Jin Y., Yang G. Circulating microRNAs predict the response to anti-PD-1 therapy in non-small cell lung cancer. Genomics. 2020;112:2063–2071. doi: 10.1016/j.ygeno.2019.11.019. - DOI - PubMed

MeSH terms

Grants and funding

This manuscript has not received external funding.