RPL22L1, a Novel Candidate Oncogene Promotes Temozolomide Resistance by Activating STAT3 in Glioblastoma

Abstract

Aggressiveness and drug resistant are major challenges in the clinical treatment of glioblastoma (GBM). Our previously research reported a novel candidate oncogene ribosomal protein L22 like 1 (RPL22L1). The aim of this study was to elucidate the potential role and mechanism of RPL22L1 in progression and temozolomide (TMZ) resistance of GBM. Online database, tissue microarrays and clinical tissue specimens were used to evaluate the expression and clinical implication of RPL22L1 in GBM. We performed cell function assays, orthotopic and subcutaneous xenograft tumor models to evaluate the effects and molecular mechanisms of RPL22L1 on GBM. RPL22L1 expression was significantly upregulated in GBM and associated with poorer prognosis. RPL22L1 overexpression enhanced GBM cell proliferation, migration, invasion, TMZ resistance and tumorigenicity, which could be reduced by RPL22L1 knockdown. Further, we found RPL22L1 promoted mesenchymal phenotype of GBM and the impact of these effects was closely related to EGFR/STAT3 pathway. Importantly, we observed that STAT3 specific inhibitor (Stattic) significantly inhibited the malignant functions of RPL22L1, especially on TMZ resistance. RPL22L1 overexpressed increased combination drug sensitive of Stattic and TMZ both in vitro and in vivo. Moreover, Stattic effectively restored the sensitive of RPL22L1 induced TMZ-resistant in vitro and in vivo. Our study identified a novel candidate oncogene RPL22L1 which promoted the GBM malignancy through STAT3 pathway. And we highlighted that Stattic combined with TMZ therapy might be an effective treatment strategy in RPL22L1 high-expressed GBM patients.

Ribosomal protein L22 like 1: a promising biomarker for lung adenocarcinoma

“…Chen et al found that RPL22L1 promoted glioblastoma resistance to temozolomide by activating STAT3 pathway. [10] Zhang et al demonstrated that RPL22L1 contributed to sorafenib resistance in hepatocellular carcinoma through the ERK signaling pathway. [11] In addition, a study by Rao indicated that RPL22L1 was associated with poor prognosis and 5-FU resistance in colorectal cancer.…”