| RRC ID |
87248
|
| Author |
Hayai S, Suzuki MM, Iijima K, Shinjo K, Murofushi Y, Xie J, Nishimura T, Ishii M, Kondo Y.
|
| Title |
A stress granule-associated RNA-binding protein FAM120A drives cisplatin resistance in non-small cell lung cancer.
|
| Journal |
J Biochem
|
| Abstract |
Cisplatin-based chemotherapy is a standard treatment for non-small cell lung cancer (NSCLC), but drug resistance poses a major clinical challenge. Stress-adaptive mechanisms, such as stress granule (SG) formation, are increasingly recognized alternative pathways that facilitate cancer cell survival. Here, we identify the RNA-binding protein, family with sequence similarity 120A (FAM120A), as an SG-associated factor that drives cisplatin resistance in NSCLC. FAM120A expression was markedly elevated in cisplatin-resistant NSCLC cell lines and clinical tumor specimens and was essential for SG formation and cell survival following cisplatin-induced stress. We found that the intrinsically disordered RNA-binding domain of FAM120A is essential for its incorporation into SGs and for its cytoprotective function. Using enhanced cross-linking immunoprecipitation sequencing data and RNA immunoprecipitation-qPCR, we identified the long noncoding RNA, metastasis-associated lung adenocarcinoma transcript 1 as a key FAM120A interacting partner. MALAT1 levels were reduced upon FAM120A depletion, and overexpression of MALAT1 was sufficient to restore cisplatin resistance in these cells. These findings suggest that MALAT1 is an RNA species that is stabilized by FAM120A and involved in the cellular response to chemotherapy. Targeting this regulatory mechanism may offer new therapeutic strategies to overcome cisplatin resistance in NSCLC.
|
| Volume |
179(2)
|
| Pages |
127-135
|
| Published |
2026-2-11
|
| DOI |
10.1093/jb/mvaf074
|
| PII |
8362612
|
| PMID |
41328536
|
| PMC |
PMC12866663
|
| MeSH |
Antineoplastic Agents* / pharmacology
Carcinoma, Non-Small-Cell Lung* / drug therapy
Carcinoma, Non-Small-Cell Lung* / genetics
Carcinoma, Non-Small-Cell Lung* / metabolism
Carcinoma, Non-Small-Cell Lung* / pathology
Cell Line, Tumor
Cisplatin* / pharmacology
Drug Resistance, Neoplasm* / drug effects
Humans
Lung Neoplasms* / drug therapy
Lung Neoplasms* / genetics
Lung Neoplasms* / metabolism
Lung Neoplasms* / pathology
RNA, Long Noncoding / genetics
RNA, Long Noncoding / metabolism
RNA-Binding Proteins* / genetics
RNA-Binding Proteins* / metabolism
Stress Granules* / metabolism
|
| Resource |
| Human and Animal Cells |
A549 |
