CircMAN1A2 promotes vasculogenic mimicry of nasopharyngeal carcinoma cells through upregulating ERBB2 via sponging miR-940

Nasopharyngeal carcinoma(NPC)is the most prevalent human primary malignancy of the head and neck,and the presence of vasculogenic mimicry(VM)renders anti-angiogenic therapy ineffective and poorly prognostic.However,the underlying mechanisms are unclear.In the present study,we used miR-940 silencing and overexpression for in vitro NPC cell EdU staining,wound healing assay and 3D cell culture assay,and in vivo xenograft mouse model and VM formation to assess miR-940 function.We found that ectopic miR-940 expression reduced NPC cell proliferation,migration and VM,as well as tumorigenesis in vivo.By bioinformatic analysis,circMAN1A2 was identified as a circRNA that binds to miR-940.Mechanistically,we confirmed that circMAN1A2 acts as a sponge for miR-940,impairs the inhibitory effect of miR-940 on target ERBB2,and then activates the PI3K/AKT/mTOR signaling pathway using RNA-FISH,dual luciferase reporter gene and rescue analysis assays.In addition,upregulation of ERBB2 expression is associated with clinical staging and poor prognosis of NPC.Taken together,the present findings suggest that circMAN1A2 promotes VM formation and progression of NPC through miR-940/ERBB2 axis and further activates the PI3K/AKT/mTOR pathway.Therefore,circMAN1A2 may become a biomarker and therapeutic target for anti-angiogenic therapy in patients with nasopharyngeal carcinoma.

Patients with Early-Stage and Estrogen Receptor-Negative Breast Cancers: Young Age Does Link to Poor Outcomes

Purpose: This study aimed to evaluate whether young adult breast cancer patients have poor outcomes independent of established prognostic factors and analyze differences in prognosis between younger and older patients stratified by tumor subtype. Methods: Of 10,950 breast cancer patients treated at West China Hospital between 1998 and 2017, 741 younger patients (Results: We identified 11 parameters (all P P P P = 0.024] and HR for DFS = 1.301 [95% CI, 1.077 - 1.572;P = 0.006]). When stratified by tumor subtype, younger patients with T1, N0, tumor stage I, G3, estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and Ki67 ≥ 14% had a poor BCSS;in addition, patients with T1, N1, tumor stages I and II, G3, ER-negative, PR-negative, and triple-negative had a poorer DFS than older patients. Conclusion: Young age was an independent prognostic factor for BCSS and DFS in breast cancer patients. The increased risk of relapse was most pronounced in early-stage breast cancer, especially in patients with ER-negative disease.