LINC01806 mediated by STAT1 promotes cell proliferation, migration, invasion, and stemness in non-small cell lung cancer through Notch signaling by miR-4428/NOTCH2 axis

Abstract

Background Non-small cell lung cancer (NSCLC), the most primary lung cancer subtype, threatens human health globally. Long non-coding RNAs (lncRNAs) have been uncovered to affect multiple cancers progression. Nevertheless, the specific function of long intergenic non-protein coding RNA 1806 (LINC01806) in NSCLC remains elusive. Methods RT-qPCR and western blot were involved in this study. The influence of LINC01806 on NSCLC was assessed by in vitro and in vivo assays. Via ChIP, RNA pull down, RIP, and luciferase reporter assays, the in-depth cellular mechanisms of LINC01806 in NSCLC were explored. Results LINC01806 expression was high in NSCLC cell lines. Functionally, LINC01806 knockdown impeded cell proliferation, migration, invasion, and stemness, along with tumor growth. As for its mechanism, signal transducer and activator of transcription 1 (STAT1) activated LINC01806 transcription in NSCLC. Furthermore, LINC01806 sequestered microRNA-4428 (miR-4428) to enhance notch receptor 2 (NOTCH2) expression, thus activating Notch signaling pathway. Finally, in vitro and in vivo assays jointly validated that LINC01806 exerted its function in NSCLC development via miR-4428/NOTCH2 pathway. Conclusion LINC01806 enhanced NOTCH2 expression to stimulate Notch signaling via sponging miR-4428, thereby facilitating NSCLC progression, which provided a novel mechanism for NSCLC therapeutic approaches. Graphical Abstract

Upregulated SPAG6 correlates with increased STAT1 and is associated with reduced sensitivity of interferon‐α response in BCR::ABL1 negative myeloproliferative neoplasms

“…Despite the results generated from most studies supporting the antineoplastic effect of STAT1, 36 accumulating evidence suggests that STAT1 also exerts a tumor-promoting function. [42][43][44] In some malignant phenotypes, STAT1 can act as an oncoprotein or tumor suppressor in the same cell type, depending on the specific genetic background. 45,46 In this present study, we found that STAT1 was highly expressed in MPN-derived leukemia cell lines.…”

Interplay between JAK/STAT pathway and non-coding RNAs in different cancers

“…There was an evident regression of the tumors developed from LINC01806-silenced NSCLC cells. However, acceleration in tumor growth was noted when NSCLC cells were co-transfected with miR-4428 antagomirs or overexpression of NOTCH2 [ 17 ].…”

Emerging roles of PHLPP phosphatases in lung cancer

“…Since the discovery of PHLPPs, a lot of studies have been conducted on illuminating of its substrates, including STAT1, MST1, S6K1 and so on (24,68,69). Although these substrates were associated with the development of lung cancer (70)(71)(72), there was no direct evidence that they were associated with PHLPPs in LC. In addition, in a global PHLPP knocked out (PHLPP -/-) mouse model, researcher has focused more on the gastrointestinal tract, including the progress of cancer and the changes of immune cells in the immune microenvironment.…”