ING2-WTAP is a potential therapeutic target in non-small cell lung cancer

Non-small-cell lung carcinoma (NSCLC) is the most common kind of lung cancer, which is also the largest cause of cancer-linked deaths globally. A lack of effective prognostic biomarkers contributes to the poor prognosis of NSCLC. For better patient outcomes, NSCLC diagnosing, prognostic, and predictive biomarkers are critically needed. A component of the chromatin-modulatory complex that dampens gene expression, ING2 (inhibitor of growth family member 2), has been linked to cellular mechanisms that enhance tumor repression. Nevertheless, its role in human NSCLC is unclear. Herein, we observed that ING2 downregulation in NSCLC tissues correlates with poor NSCLC prognosis. Functional analysis illustrated that ING2 dampened growth, infiltration along with metastasis and blocked apoptosis of NSCLC cells in vitro, as well as in vivo. The mechanism might be implicated in the EMT (epithelial-mesenchymal transition) process. Mechanistically, we found that ING2 silencing suppresses the expressions of Wilms tumor 1-associated protein (WTAP) and that WTAP expression negatively correlates with ING2 expression. Moreover, rescue experiments illustrated that WTAP overexpression partially counteracts the effect of ING2 silencing on proliferation. Finally, we found that elevated WTAP levels correlate with poor NSCLC prognosis. These results highlight the prognostic and therapeutic potential of ING2-WTAP in NSCLC. (C) 2022 Elsevier Inc. All rights reserved.

Automated summary

A study found that downregulation of ING2 is associated with poor prognosis in non-small-cell lung carcinoma (NSCLC). Experimental results showed that ING2 can inhibit the growth, infiltration, metastasis, and promote apoptosis of NSCLC cells, possibly through the epithelial-mesenchymal transition (EMT) process. Further research revealed that ING2 silencing suppressed the expression of Wilms tumor 1-associated protein (WTAP), and overexpression of WTAP partially counteracted the effect of ING2 silencing on cell proliferation. In addition, elevated levels of WTAP were correlated with poor prognosis in NSCLC.