HMG-box transcription factor 1: a positive regulator of the G1/S transition through the Cyclin-CDK-CDKI molecular network in nasopharyngeal carcinoma.

HMG-box transcription factor 1 (HBP1) has been reported to be a tumor suppressor in diverse malignant carcinomas. However, our findings provide a conclusion that HBP1 plays a novel role in facilitating nasopharyngeal carcinoma (NPC) growth. The Kaplan-Meier analysis indicates that high expression HBP1 and low miR-29c expression both are negatively correlated with the overall survival rates of NPC patients. HBP1 knockdown inhibits cellular proliferation and growth, and arrested cells in G1 phase rather than affected cell apoptosis via flow cytometry (FCM) analysis. Mechanistically, HBP1 induces the expression of CCND1 and CCND3 levels by binding to their promoters, and binds to CDK4, CDK6 and p16INK4A promoters while not affects their expression levels. CCND1 and CCND3 promote CCND1-CDK4, CCND3-CDK6, and CDK2-CCNE1 complex formation, thus, E2F-1 and DP-1 are activated to accelerate the G1/S transition in the cell cycle. MiR-29c is down-regulated and correlated with NPC tumorigenesis and progression. Luciferase assays confirms that miR-29c binds to the 3' untranslated region (3'-UTR) of HBP1. Introduction of pre-miR-29c decreased HBP1 mRNA and protein levels. Therefore, the high endogenous HBP1 expression might be attributed to the low levels of endogenous miR-29c in NPC. In addition, HBP1 knockdown and miR-29c agomir administration both decrease xenograft growth in nude mice in vivo. It is firstly reported that HBP1 knockdown inhibited the proliferation and metastasis of NPC, which indicates that HBP1 functions as a non-tumor suppressor gene in NPC. This study provides a novel potential target for the prevention of and therapies for NPC.