miR-31 Displays Subtype Specificity in Lung Cancer

Abstract

miRNA rarely possess pan-oncogenic or tumor-suppressive properties. Most miRNAs function under tissue-specific contexts, acting as either tumor suppressors in one tissue, promoting oncogenesis in another, or having no apparent role in the regulation of processes associated with the hallmarks of cancer. What has been less clear is the role of miRNAs within cell types of the same tissue and the ability within each cell type to contribute to oncogenesis. In this study, we characterize the role of one such tissue-specific miRNA, miR-31, recently identified as the most oncogenic miRNA in lung adenocarcinoma, across the histologic spectrum of human lung cancer. Compared with normal lung tissue, miR-31 was overexpressed in patient lung adenocarcinoma, squamous cell carcinoma, and large-cell neuroendocrine carcinoma, but not small-cell carcinoma or carcinoids. miR-31 promoted tumor growth in mice of xenografted human adenocarcinoma and squamous cell carcinoma cell lines, but not in large- or small-cell carcinoma lines. While miR-31 did not promote primary tumor growth of large- and small-cell carcinoma, it did promote spontaneous metastasis. Mechanistically, miR-31 altered distinct cellular signaling programs within each histologic subtype, resulting in distinct phenotypic differences. This is the first report distinguishing diverse functional roles for this miRNA across the spectrum of lung cancers and suggests that miR-31 has broad clinical value in human lung malignancy. Significance: These findings demonstrate the oncogenic properties of miR-31 in specific subtypes of lung cancer and highlight it as a potential therapeutic target in these subtypes.

Promising Biomarkers in Head and Neck Cancer: The Most Clinically Important miRNAs

“…The literature on miR-31 is quite controversial, as this particular miRNA appears to be downregulated in certain types of cancer, such as liver [ 137 ], prostate [ 138 ], and triple negative breast cancer [ 139 ], but upregulated in colorectal [ 140 ], cervical [ 141 ], rectal [ 142 ], and certain subtypes of lung cancer [ 143 ], suggesting that the mode of miR-31 regulation depends on cancer histology. Overall, in HNC, miR-31 mostly appears to be upregulated [ 46 , 47 , 79 , 144 , 145 , 146 ], acting as an oncogene and promoting the proliferation and invasion of tumor cells [ 147 ].…”

plasma: Partial LeAst Squares for Multiomics Analysis

“…The highest-weight microRNAs in the model correspond to hsa-miR-31, which is associated in our data with shorter survival. This miR is known to promote tumor growth and correlates with low survival in previous studies (Davenport et al 2021; Edmonds et al 2016; Tan et al 2011). By contrast, hsa-miR-34 is associated in our model with longer survival.…”

The EGFR Signaling Modulates in Mesenchymal Stem Cells the Expression of miRNAs Involved in the Interaction with Breast Cancer Cells

“…This phenomenon can be explained because a single miRNA triggers a variety of targets that in turn activate different signaling pathways. Indeed, a recent study demonstrated that miR-31 had different functional roles across lung cancer subtypes by activating different signaling pathways [ 32 ].…”