HnRNPR-CCNB1/CENPF axis contributes to gastric cancer proliferation and metastasis

Abstract

Gastric cancer (GC) is a common disease globally with high mortality rate. It is therefore necessary to develop novel therapies targeting specific events in the pathogenesis of GC. Some hnRNP family members are involved in multiple cancer biological behaviors. However, the potential function and mechanism of hnRNPR, a new molecule of hnRNP family in GC remains unknown. We found that the expression of hnRNPR was significantly overexpressed in multiple cancers compared to the normal tissues. Functionally, hnRNPR promoted cancer cell proliferation, migration, and invasion. Knockdown of hnRNPR in two type mice models, with two types of tumors models decreased the tumor aggressiveness and metastasis. Mechanistically, hnRNPR targeted oncogenic pathways by stabilizing the expression of CCNB1 and CENPF mRNA level. Knockdown of CCNB1 and CENPF abolished the hnRNPR-induced cell growth and invasion, respectively. Furthermore, the protein level of hnRNPR in the tumor was positively correlated with the expression of CCNB1 and CENPF in clinical samples. Together, these results indicate that overexpression of hnRNPR promoted the aggressiveness of GC by increasing the mRNA expression of CCNB1 and CENPF. HnRNPR-CCNB1/CENPF axis may be a potential therapeutic target for GC treatment.

TOP2A and CENPF are synergistic master regulators activated in cervical cancer

“…To date, there is no reported functional role of CENPF implicated in CC. However, CENPF was reported to be overexpressed, drive tumorigenesis and/or associated with poor prognosis in several human malignancies, including breast cancer [40], prostate cancer [41][42][43][44], bladder cancer [45], gastric cancer [46], hepatocellular carcinoma [47][48][49], pancreatic carcinoma [50]. In this study, higher CENPF expression was found to be significantly associated with metastasis compared to CC tissues (Fig.…”

“…Small molecule compounds targeting CENPF have not been reported, possibly attributed by the difficulty to target a non-enzyme target. However, reports have shown that silencing CENPF using in vitro models abolished invasion in gastric cancer [46], resulted in the cell cycle arrest at G2/M checkpoint in hepatocellular carcinoma [47], reduced levels of epithelialmesenchymal transition markers, inhibited cell proliferation, migration, and invasion, reduced global bioenergetic capacity and altered the global metabolic profiles in prostate cancer [43,53]. It remained to be validated whether silencing/inhibiting either CENPF or both CENPF and TOP2A will have a strong phenotypic consequence in CC using an in-vitro or/and in vivo model.…”

Overexpression of CENPF is associated with progression and poor prognosis of lung adenocarcinoma

“…According to previous studies, MCM3AP-AS1 could hasten tumor growth in breast cancer by targeting CENPF via competitively binding to miR-28-5p 17 . Besides, overexpression of hnRNPR promoted the aggressiveness of gastric cancer by increasing the mRNA expression of CCNB1 and CENPF 18 . Maybe the molecular mechanisms underlying the effects of CENPF on the oncogenesis of LUAD also could be regulated by noncoding RNAs.…”

LDLRAD2 overexpression predicts poor prognosis and promotes metastasis by activating Wnt/β-catenin/EMT signaling cascade in gastric cancer

“…However, not all patients could benefit from anti-HER2 or anti-VEGFR monoclonal antibody and the monoclonal antibodies are not suitable for GC patients with negative HER2 or VEGFR expression [12]. Therefore, it is imperative to further elucidate the molecular mechanisms underlying GC invasion and metastasis fully so as to identify novel effective therapeutic targets [13].…”