Fig. 8

SOCS1 is indispensable for tumor-promoting function of LINC00669 in vivo. a, Tumor growth curves as recorded by measuring tumor volume. Depletion of LINC00669 hampered xenograft tumor growth in nude mice, which could be partially rescued by simultaneous knockdown of SOCS1 in NPC cells. NC, negative control; siLINC, siRNA-mediated silencing of LINC00669; siSOCS1, siRNA-mediated silencing of SOCS1. b, Representative images showing xenograft tumors. c, IHC results showing the number of proliferating (Ki67⁺) cells was decreased in tumors derived from LINC00669-depleted NPC cells, where the number of apoptotic (Caspase 3⁺) cells was increased accordingly. In contrast, simultaneous knockdown of SOCS1 in the LINC00669-depleted NPC cells restored cell proliferation and suppressed apoptosis in the xenograft tumors. d, The activation of JAK/STAT signaling pathway is under tight control of SOCS1 in normal cells. The growth homeostasis is interrupted due to the aberrant expression of LINC00669. Mechanistically, abnormal accumulation of cytosolic LINC00669 competitively binds to SOCS1, and insulates it from touching the transcription factor STAT1 for ubiquitination modification, which stabilizes STAT1 and promotes further phosphorylation by escaping from the proteasomal degradation. The activated STAT1 then enters the nuclei and initiates the transcriptional program associated with cell proliferation and invasion