M6A associated TSUC7 inhibition contributed to Erlotinib resistance in lung adenocarcinoma through a notch signaling activation dependent way.

ABSTRACT:

Background

The small tyrosine kinase inhibitors (TKIs) subversively altered the lung cancer treatments, but patients will inevitably face the therapy resistance and disease recurrence. We aim to explore the potential roles of non-coding RNAs in sensitizing the TKIs effects.

Methods

Multiple cellular and molecular detections were applied to confirm the mechanistic regulations and intracellular connections.

Results

We explored the specific gene features of candidates in association with resistance, and found that m6A controlled the stemness of EMT features through METTL3 and YTHDF2. The miR-146a/Notch signaling was sustained highly activated in a m6A dependent manner, and the m6A regulator of YTHDF2 suppressed TUSC7, both of which contributed to the resistant features.

SUBMITTER: Li K 

PROVIDER: S-EPMC8520306 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature