Plac8‐mediated autophagy regulates nasopharyngeal carcinoma cell function via AKT/mTOR pathway

Abstract

To explore the relationship between autophagy and cell function, we investigated how PLAC8‐mediated autophagy influences proliferation, apoptosis and epithelial‐mesenchymal transition (EMT) in NPC. Colony formation analyses and CCK8 assays were used to assess the proliferative capacity of NPC cells. Transmission electron microscopy (TEM) was used to identify autophagosomes. Autophagic flux was monitored using the tandem monomeric RFP‐GFP‐tagged LC3 (tfLC3) assay. The rate of apoptosis in NPC cells was analysed by flow cytometry. Western blot analysis was used to evaluate the activation of autophagy and the signalling status of the AKT/mTOR pathway. Our study reveals that knocking out PLAC8 (koPLAC8) induces autophagy and apoptosis, while suppressing NPC cell proliferation and EMT. However, inhibition of autophagy with 3‐methyladenine or by knocking down Beclin‐1 reverses the cell proliferation, apoptosis and EMT influenced by koPLAC8. We find that koPLAC8 inhibits the phosphorylation of AKT and its downstream target, mTOR. Moreover, immunofluorescence and co‐immunoprecipitation reveal complete PLAC8/AKT colocalization and PLAC8/AKT interaction, respectively. Furthermore, knockout of PLAC8 induced autophagy and inactivated AKT/mTOR signalling pathway of NPC xenografts. Overall, our findings demonstrate that koPLAC8 induces autophagy via the AKT/mTOR pathway, thereby inhibiting cell proliferation and EMT, and promoting apoptosis in NPC cells.

Identification of Autophagy- and Ferroptosis-Related lncRNAs Functioned through Immune-Related Pathways in Head and Neck Squamous Carcinoma

“…The majority of the DEGs, e.g., SOX11 , TBX21 , FAM3B , FGF5 , HNF1A , MYB , and PLAC8 have been reported to function as promoters or biomarkers in various cancer types [ 44 , 45 , 46 , 47 , 48 , 49 , 50 ]. Among these, PLAC8 were found to regulate autophagy-related functions in a variety of cancers [ 51 , 52 ]. In addition, numerous DEGs were reported to be involved in the proliferation and differentiation of immune cells and could regulate immune functions, including CD226 , IRF4 , LY9 , MS4A1 , TBX21 , TNFRSF17 , FCRLA , and SLAMF6 [ 45 , 53 , 54 , 55 , 56 , 57 , 58 ].…”

“…Life 2021, 11, x FOR PEER REVIEW 9 of 18 in a variety of cancers [51,52]. In addition, numerous DEGs were reported to be involved in the proliferation and differentiation of immune cells and could regulate immune functions, including CD226, IRF4, LY9, MS4A1, TBX21, TNFRSF17, FCRLA, and SLAMF6 [45,[53][54][55][56][57][58].…”

PLAC8 promotes the autophagic activity and improves the growth priority of human trophoblast cells

“…Present data corroborated the finding that PLAC8 promotes autophagosome‐lysosome fusion 12 and extended the mechanisms of PLAC8‐induced autophagy. Previous reports noted PLAC8 mediated the signaling status of the AKT/mTOR pathway, NF‐κβ activity, and induce apoptosis in cancer cells 12,39 . However, we identified AMPK/Lkb1 pathway activation is involved, and characterized features of autophagy‐related protein as ATG12, Beclin‐1.…”

Silencing of NACC1 inhibits the proliferation, migration and invasion of nasopharyngeal carcinoma cells via regulating the AKT/mTOR signaling pathway

“…3A, NACC1 silencing significantly inhibited the phosphorylation of AKT and mTOR. Subsequently, SC79, an activator of AKT (12), was used to treat cells in which NACC1 was knocked down. The results presented in Fig.…”

“…mTOR functions as an oncogene in several types of cancer, including NPC, and the activation of the AKT/mTOR signaling pathway has been largely reported to be associated with cell activities, such as proliferation, migration and invasion (11,12). Notably, NACC1 can promote cell viability and inhibit the apoptosis of retinoblastoma cells via activating the AKT/mTOR signaling pathway (13).…”