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

Abstract

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.

Is the Secret of VDAC Isoforms in Their Gene Regulation? Characterization of Human VDAC Genes Expression Profile, Promoter Activity, and Transcriptional Regulators

“…The results of P VDAC3 analysis ( Table 4 ) showed a distribution of binding sites for TFs involved in the control of various cellular processes including cell differentiation, proliferation, apoptosis, and gametogenesis: V$BCL6 (BED subclass of zinc-finger proteins), a critical regulator of B cell differentiation [ 62 ]; V$CDXF (Vertebrate caudal related homeodomain protein) involved in development and maintenance of trophectoderm [ 63 ]; V$FOX (Forkhead (FKH)/Forkhead box (Fox)), including important regulators of development, organogenesis, metabolism, and cell homeostasis [ 64 ]; V$SOHLH (Spermatogenesis and oogenesis basic helix–loop–helix) transcription regulators of male and female germline differentiation [ 65 ]; V$HMG (High-Mobility Group family), including factors that regulate neuronal differentiation and also play important roles in tumorigenesis [ 66 ]; V$HOMF (Homeodomain transcription factors) involved in central nervous development [ 67 ]; V$IRFF (Interferon regulatory factors) required for differentiation of hematopoietic cells [ 68 ]; V$LBXF (Ladybird homeobox (lbx) gene family) that plays a critical role in embryonic neurogenesis and myogenesis and in muscle mass determination [ 69 ]; V$MYBL (cellular and viral myb-like transcriptional regulators) that controls cell cycle progression, survival, and differentiation [ 70 ]; V$SMAD (Vertebrate SMAD family of transcription factors) that includes factors responsible for several cellular processes, including proliferation, differentiation, apoptosis, migration, as well as cancer initiation and progression [ 71 ]; V$XBBF (X-box binding factors) family involved in the control of development and maintenance of the endoplasmic reticulum (ER) in multiple secretory cell lineages [ 72 ].…”

AR-induced long non-coding RNA LINC01503 facilitates proliferation and metastasis via the SFPQ-FOSL1 axis in nasopharyngeal carcinoma

“…The ChIP assay was performed using the Pierce ™ Magnetic ChIP Kit (Thermo Fisher Scientific) according to the manufacturers’ instructions as previously described [ 47 ]. The purified short clip DNA was detected using specific FOSL1 or LINC01503 promoter region primers as monitored by qPCR.…”

Advances in targeted therapy mainly based on signal pathways for nasopharyngeal carcinoma

“…215 Arresting cell at G1/S-phase and inhibiting the proliferation of NPC cells by miR-29c can be achieved by reduction of the transcription factor HMG-box transcription factor 1 (HBP1), causing the downregulation of cyclin D1 and cyclin D3. 216 MiR-185-3p and miR-324-3p regulate the growth and apoptosis of NPC, which can be partially achieved by targeting the 3′-UTR of SMAD7. 217 Promotion of cancer Conversely, some miRNAs and lncRNAs are upregulated in cancer tissues and facilitate pathological activities related to NPC, including inhibition of apoptosis, promotion of tumor cell proliferation, invasion, and metastasis.…”