<p>High expression of NUCB2 promotes papillary thyroid cancer cells proliferation and invasion</p>

Abstract

Background NUCB2, a novel multifunctional protein containing several functional domains, was newly found to play important roles in many cancers, but its role in papillary thyroid cancer (PTC) is not well investigated. Therefore, our study was performed to explore the functions of NUCB2 in PTC. Methods NUCB2 protein level was analyzed by immunohistochemistry. Data analyses were made by performing chi-squared test. Quantitative reverse-transcription PCR, Western blot, colony formation, MTT, and transwell invasion assays were performed to test the expression levels and functions of NUCB2 in PTC. Results In PTC tissues, NUCB2 protein expression level was positively correlated with extrathyroidal extension, TNM stage, and tumor size of PTC patients. In vitro experiments demonstrated that knockdown of NUCB2 using specific shRNA for NUCB2 significantly impaired cell proliferation and invasion of PTC cell lines. In vivo, silencing of NUCB2 inhibited the growth of tumors in mice. Conclusion These results suggested a novel function of NUCB2 in the process of proliferation and invasion in PTC. NUCB2 may be considered a potent prognostic factor in PTC.

The Multifaceted Nature of Nucleobindin-2 in Carcinogenesis

“…The expression levels of MMP-2 and MMP-9 in bladder cancer cells transfected with Nucb2 shRNA was lowered, indicating that Nucb2 may affect cancer migration and invasion through the MMP-2 and MMP-9 signaling pathways [ 26 ]. Analogous correlation was also recently found in papillary thyroid tumor cells [ 20 ], as well as previously for breast [ 13 ], renal [ 21 ], and colon [ 19 ] cancer cells. Similarly, in endometrial carcinoma cells [ 14 ], Nucb2 and its derivative nesfatin-1 significantly induced cell proliferation and migration.…”

“…Despite the fact that its broad physiological function has been extensively investigated, there is also growing evidence that Nucb2 may play an important role in the multistep processes of tumorigenesis. A high expression of Nucb2, in comparison to adjacent non-cancerous cells, was found in breast [ 13 ], prostate [ 12 ], colon [ 19 ], endometrial [ 14 ], papillary thyroid [ 20 ], and renal cell carcinomas [ 21 ]. The immunoreactivity of Nucb2 was mainly detected in the cytoplasm of cancer cells [ 13 , 22 , 23 ].…”

“…Similarly, in endometrial carcinoma cells [ 14 ], Nucb2 and its derivative nesfatin-1 significantly induced cell proliferation and migration. 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 ].…”

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

“…No relationship was found between NUCB2/NESF-1 and age, gender, or lymph node metastasis. [ 53 ]. Bearing in mind the above, it was speculated that NUCB2/NESF-1 could be a tumor promoter in papillary thyroid cancer.…”

“…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.…”