Sperm-associated antigen 9 is upregulated in hepatocellular carcinoma tissue and enhances QGY cell proliferation and invasion in�vitro

Abstract

Abstract.The incidence and mortality rates of hepatocellular carcinoma (HCC) are higher in China compared with in other countries. Further research is required in order to improve the diagnosis and treatment of HCC. Sperm-associated antigen 9 (SPAG9) protein has been revealed to serve an important function in cancer progression; however, the underlying mechanisms remain to be elucidated. The present study investigated the expression level of SPAG9 in HCC tissues using quantitative-polymerase chain reaction, immunohistochemistry and western blotting, and the results demonstrated that SPAG9 was overexpressed in HCC tissues compared with the adjacent non-cancerous tissues. To explore the potential mechanisms underlying SPAG9 in HCC, the effect of SPAG9 on cell proliferation, cell cycle, migration and invasion capacities were investigated in the QGY HCC cell line by RNA interference. It was revealed that inhibition of SPAG9 mRNA in QGY cells significantly inhibited the expression level of SPAG9 compared with the control. Depletion of SPAG9 expression decreased cell proliferation (P<0.01) and increased the percentage of cells in the G 1 /G 2 cell cycle phase. The percentage of cells in the S phase was decreased, and cell migration and invasion capabilities in vitro were reduced (P<0.01). In summary, the results of the present study suggested that SPAG9 was upregulated in HCC and may serve an important function in cancer cell proliferation, differentiation and invasion. Whether SPAG9 is a potential diagnostic marker and therapeutic target of human HCC requires additional study. IntroductionSperm-associated antigen 9 (SPAG9) has characteristics of a scaffold protein and is involved in the c-Jun N-terminal kinase JNK signaling pathway, binding to JNK, which suggests that it is involved in physiological processes, including apoptosis, survival, proliferation and tumorigenesis (1,2). SPAG9 is a member of the cancer/testis antigen family expressed from a single copy gene located on human chromosome 17q21. Proteins in the cancer/testis antigen family are overexpressed in a variety of types of cancer (3,4). SPAG9 is also expressed in a variety of tumors (5-9). SPAG9 has been proposed as a novel biomarker for early diagnosis of multiple human tumors, including ovarian, cervical and breast cancers (10-12). Certain studies have revealed that small interfering RNA inhibits expression of SPAG9 and inhibits the growth of various types of tumor cells (13,14). SPAG9 protein has been demonstrated to be involved in cancer progression; however, the underlying mechanisms remain unknown (15,16).Hepatocellular carcinoma (HCC) is the sixth most common type of cancer globally and is the third most common cause of cancer-associated mortality (17). The incidence of HCC is higher in South East Asia and Africa compared with other regions of the world (18). The crucial etiological factors involved in the development of HCC include infection with hepatitis virus, the structural or functional mutation of oncogenes and tumor suppressor genes (19-21...

SPAG9 Expression Predicts Good Prognosis in Patients with Clear-Cell Renal Cell Carcinoma: A Bioinformatics Analysis with Experimental Validation

“…We carefully reviewed previous studies on the role of SPAG9 in different tumor-cell lines and summarized the results [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ] ( Table S5 ). We noted that in addition to promoting proliferation, migration, and EMT, SPAG9 also promotes autophagy in several tumor-cell lines [ 18 , 19 ].…”

“…Sperm-associated antigen 9 ( SPAG9 ) is a cancer-testis antigen expressed in various tumor tissues, which has two main alternative spliceosomes—JLP (1307 amino acids) and SPAG9 (766 amino acids). It plays a wide role in tumor-cell lines: it not only promotes proliferation, migration, and epithelial–mesenchymal transition (EMT) [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ], but also regulates autophagy [ 18 , 19 ]. A previous study found that SPAG9 overexpression promotes proliferation and migration in the ccRCC cell lines Caki-1 and NII-AKS413 [ 4 ]; however, studies on the prognostic value of SPAG9 in ccRCC patients are still lacking.…”

SPAG9/MKK3/p38 axis is a novel therapeutic target for liver cancer

“…6, left panel). Notably, our previous study discovered that SPAG9 depletion caused cell cycle arrest in the G1-G2 phase in QGY-7703 cells (10); however, in HepG2 cells, the cell cycle was arrested in the S phase. We speculated that this difference is due to the different types of liver cancer from which these two cell lines were derived: QGY-7703 cells were derived from a hepatocellular carcinoma, but HepG2 cells were derived from a hepatoblastoma (19), and the specific regulatory mechanism of SPAG9 in the cell cycle and apoptosis requires further exploration.…”

“…It can be overexpressed in tumors of the ovary, breast, lung and bone (5)(6)(7), and the expression of SPAG9 in tumor tissues is correlated with progression and prognosis of cancer patients (8,9). We previously demonstrated that SPAG9 was overexpressed in liver cancer (10), however, how SPAG9 influences liver cancer progression is not yet clear. In the present study, we analyzed the function of SPAG9 in the liver cancer-derived HepG2 cells.…”

Oncolytic adenovirus carrying SPAG9-shRNA enhanced the efficacy of docetaxel for advanced prostate cancer

“…Sperm-associated antigen 9 (SPAG9) gene is located on human chromosome 17q21.33 and encodes a protein of 766 amino acids that is highly expressed in cancer and contributes to the occurrence and development of tumors [8][9][10]. Moreover, silencing of SPAG9 inhibited liver cancer, cervical cancer and kidney cancer [10][11][12].…”