Nucleobindin-2 Promotes the Growth and Invasion of Glioblastoma

Abstract

Background: Glioblastoma is one of the most malignant tumors in the brain with high mortality. In recent years, immunotherapy and targeted therapy show great prospects in the treatments for glioblastoma, whereas more effective therapeutic targets are still urgently needed to be developed. Nucleobindin-2 (NUCB2) is the precursor protein of nesfatin-1, which have a variety of metabolic functions, such as food intake and temperature regulation. In recent years, the potential link between NUCB2 and the development of multiple cancer was gradually revealed; however, the effects of NUCB2 on the progression of glioblastoma are still unclear. Methods: Immunohistochemical assays were performed to explore the NUCB2 expression levels in 94 samples of glioblastoma and corresponding nontumor tissues; patients were divided into NUCB2 high expression group and low expression group. Clinical analysis related to the clinical features, the potential link between NUCB2 expression levels, and clinical features were analyzed; the effects of NUCB2 on cell proliferation and invasion of glioblastoma were detected through colony formation and MTT assay, and transwell assay respectively. The possible effects of NUCB2 on tumor growth and metastasis were measured in mice. Results: In this study, we demonstrated that NUCB2 over-expression was correlated with the high degree of recurrence of patients with glioblastoma. Further, we also revealed that NUCB2 promoted cell proliferation and invasion of glioblastoma in vitro and promoted the growth and metastasis of glioblastoma in mice. Conclusion:This study provided evidence that NUCB2 might be a novel therapeutic target of glioblastoma.

Nucleobindin-2/Nesfatin-1—A New Cancer Related Molecule?

“…Liu et al found that the mRNA expression level of NUCB2/NESF-1 in glioblastoma was significantly higher than in normal tissues ( p < 0.05, n = 163) [ 58 ]. The IHC staining showed that NUCB2/NESF-1 was predominantly expressed in the nucleus and was highly overexpressed in glioblastoma compared to the adjacent tissue [ 58 ]. Moreover, it was noticed that the high expression of NUCB2/NESF-1 was related to the recurrence.…”

“…As a result, there is a need to identify new proliferation-related molecules in cancers. In vitro studies showed that NUCB2/NESF-1 knockdown with siRNA or shRNA in breast cancer (MCF-7, SKBR-3), bladder cancer (T24, 5637), glioblastoma (U251, U87), endometrial cancer (Ishikawa and Sawano), and thyroid cancer (TPC-I, KI) cell lines resulted in the inhibition of cell proliferation [ 41 , 47 , 50 , 53 , 58 ]. Moreover, proliferation-related proteins (Ki-67 and PCNA) were decreased in NUCB2/NESF-1 shRNA-transfected thyroid cancer cells compared to the control.…”

“…To evaluate the role of NUCB2/NESF-1 related to the growth and metastasis of glioblastoma, NUCB2/NESF-1-silenced cells were injected into nude mice. The findings indicated that the NUCB2/NESF-1 ablation group’s tumor volume was significantly smaller than the control [ 58 ]. Additionally, NUCB2/NESF-1 knockdown in the 786-O renal cancer cell line inhibited cell proliferation by arresting the cell cycle at the S phase.…”

The Multifaceted Nature of Nucleobindin-2 in Carcinogenesis

“…The immunoreactivity of Nucb2 was mainly detected in the cytoplasm of cancer cells [ 13 , 22 , 23 ]. However, in glioblastoma cancer cells [ 24 ], the localization of Nucb2 was nuclear. In most cases, Nucb2 expression was correlated with the key clinicopathological characteristics of cancer.…”

“…Moreover, in vivo studies also showed that the knockdown of Nucb2 might decrease tumor growth, at least in the case of thyroid and bladder cancer cells [ 20 , 26 ]. In addition, lung metastases were not observed in cells with Nucb2 suppression [ 24 , 26 ]. All of the above-mentioned analyses indicate that Nucb2 is linked in a tissue-specific manner to tumor development and metastasis, both in vitro and in vivo.…”