# MRPL35 Induces Proliferation, Invasion, and Glutamine Metabolism in NSCLC Cells by Upregulating SLC7A5 Expression

## TL;DR

This study shows that MRPL35 promotes lung cancer cell growth and metabolism by increasing SLC7A5 levels, suggesting it could be a new treatment target.

## Contribution

The study reveals a novel mechanism where MRPL35 promotes NSCLC progression via SLC7A5 upregulation and glutamine metabolism.

## Key findings

- MRPL35 is highly expressed in NSCLC and correlates with poor patient outcomes.
- MRPL35 knockdown reduces cancer cell proliferation, invasion, and glutamine metabolism.
- SLC7A5 overexpression rescues the anticancer effects of MRPL35 silencing.

## Abstract

Mitochondrial ribosomal protein L35 (MRPL35) has been reported to contribute to the growth of non–small cell lung cancer (NSCLC) cells. However, the functions and mechanisms of MRPL35 on glutamine metabolism in NSCLC remain unclear.

The detection of mRNA and protein of MRPL35, ubiquitin‐specific protease 39 (USP39), and solute carrier family 7 member 5 (SLC7A5) was conducted using qRT‐PCR and western blotting. Cell proliferation, apoptosis, and invasion were evaluated using the MTT assay, EdU assay, flow cytometry, and transwell assay, respectively. Glutamine metabolism was analyzed by detecting glutamine consumption, α‐ketoglutarate level, and glutamate production. Cellular ubiquitination analyzed the deubiquitination effect of USP39 on MRPL35. An animal experiment was conducted for in vivo analysis.

MRPL35 was highly expressed in NSCLC tissues and cell lines, and high MRPL35 expression predicted poor outcome in NSCLC patients. In vitro analyses suggested that MRPL35 knockdown suppressed NSCLC cell proliferation, invasion, and glutamine metabolism. Moreover, MRPL35 silencing hindered tumor growth in vivo. Mechanistically, USP39 stabilized MRPL35 expression by deubiquitination and then promoted NSCLC cell proliferation, invasion, and glutamine metabolism. In addition, MRPL35 positively affected SLC7A5 expression in NSCLC cells in vitro and in vivo. Moreover, the anticancer effects of MRPL35 silencing could be rescued by SLC7A5 overexpression in NSCLC cells.

MRPL35 expression was stabilized by USP39‐induced deubiquitination in NSCLC cells, and knockdown of MRPL35 suppressed NSCLC cell proliferation, invasion, and glutamine metabolism in vitro and impeded tumor growth in vivo by upregulating SLC7A5, providing a promising therapeutic target for NSCLC.

SLC7A5 overexpression reversed MRPL35 knockdown‐caused inhibition of NSCLC cell growth, invasion, glutamine metabolism, and induction of cell apoptosis.