LINC00669 insulates the JAK/STAT suppressor SOCS1 to promote nasopharyngeal cancer cell proliferation and invasion

Abstract

Nasopharyngeal carcinoma (NPC) is an epithelial cancer emerging from the lining of nasopharyngeal mucosa, with extremely frequent occurrence in east and southeast Asia. For the purpose of exploring roles of the dysregulated long non-coding RNA (lncRNA) in NPC, we identified a novel lncRNA LINC00669 with an apparent negative correlation to the overall survival from human NPC mRNA expression profiling databases. We further performed RNA pulldown coupled with mass spectrum to find out its target protein, and applied a series of in vitro and in vivo loss-and-gain-of function assays to investigate its oncogenic roles in NPC tumor development and progression. Our results demonstrated that LINC00669 competitively binds to the key JAK/STAT signaling pathway suppressor SOCS1, and insulates it from imposing ubiquitination modification on the pathway component of STAT1, which leads to its abnormal stabilization and activation. The activated STAT1 is then transferred into the nucleus and initiates the transcription of genes related to proliferation and invasion. In summary, our study reveals that the cytoplasmic resident lncRNA LINC00669 confers malignant properties on NPC cancer cells by facilitating a persistent activation of the JAK/STAT signaling pathway. Findings in the current study shed lights on prospects for treating NPC using strategies targeting the novel regulator of the JAK/STAT signaling.

Ferroptosis Driver SOCS1 and Suppressor FTH1 Independently Correlate With M1 and M2 Macrophage Infiltration in Head and Neck Squamous Cell Carcinoma

“…Moreover, loss of SPTBN1 expression induces liver cancer through downregulation of SOCS1 expression as well (Lin et al, 2021). In nasopharyngeal carcinoma, LINC00669 protects SOCS1 from ubiquitinating STAT1, which promotes cancer cell proliferation and invasion (Qing et al, 2020). Here we show that SOCS1 was differentially expressed at higher levels in HNSCC and served as a significant and independent prognostic factor for HNSCC, consistent with its role in hepatocellular carcinoma (Khan et al, 2020).…”

Linc01513 inhibits the malignant potential of Nasopharyngeal carcinoma by binding to PTBP1

“…LncRNA AFAP1-AS1 can regulate the integrity of cellular myofibroids and regulate cytoskeletal remodeling by changing the expression level of AFAP1 protein, thus promoting the invasion and metastasis of nasopharyngeal carcinoma cells 22 . In addition, lncRNA FOXD1-AS1, RP11-624L4.1 and linc00669 play diverse roles in the occurrence and development of nasopharyngeal cancer 23 - 25 . In this study, the GEO database dataset GSE61218 was used to screen and the linc01513 expression was significantly lower.…”

Long noncoding RNAs: fine-tuners hidden in the cancer signaling network

“…In this way, LINC00669 protects STAT1 from ubiquitination modification and stabilizes it. STAT1 translocates to the nucleus and promotes the transcription of target genes [ 84 ]. Meanwhile, tumor-suppressive lncRNAs, such as RP11-468E2.5, suppress the JAK/STAT signaling pathway by targeting STAT5 and STAT6, thereby inhibiting colorectal cancer cell proliferation and promoting apoptosis [ 85 ].…”