AURKA, also known as aurora kinases, belongs to serine/threonine kinases which share a highly conserved catalytic domain containing auto phosphorylating sites [16]. It positively regulates cell cycle progression and plays a role in the cell centrosome and the spindle microtubules during mitosis [17], which implied that AURKA maybe promotes cancer cell division. On the other hand, it has been widely reported that AURKA is an oncogene to promote tumorigenesis in multiple types of cancer including solid tumors and hematological malignancies [16], such as bladder cancer [18, 19], prostate cancer [20, 21], colon cancer [22].
CCNB1 is a regulatory protein involved in mitosis and a critical cell cycle regulator of the G2/M checkpoint [23]. Previous studies have reported that CCNB1 could participate in oncogene pathways among many kinds of cancers, BC, colorectal cancer [24-27]. And initial stage of cancer, it was more recognized by the T cells [11, 28]. In this study, we found CCNB1 was up-regulated in BC and associated with poor survival.
BUB1B, also called mitotic checkpoint serine/threonine-protein kinase BUB1 beta, is an important element of the mitotic checkpoint [29]. It plays a potential role in spindle checkpoint function in many kinds of cancer [30]. It has reported that inhibited BUB1B leading to cell death, and grow slowly in BC cell [31], consistent with our study.
PRC1(Polycomb Repressive Complexes 1), PRC2 could form a multicomponent complex with PRC2, and these complexes play many roles in the biological process, such as pluripotency, development, and carcinogenesis et al. The abnormal regulation of PRC1 had contributed to cancer progress [32, 33], also some research has confirmed that in prostate cancer and breast cancer [34, 35]. But the mechanism of PRC1 in cancer still unclear.
Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein. The expression of TPX2 is strictly regulated by the cell cycle. In general, TPX2 exists in the G1 and S phases of the cell cycle and disappears at the end of cytokinesis [36]. A growing number of papers reported that the high expression of TPX2 was connected with bad and shorter overall survival of patients in many tumors [37-39], but the mechanism of TPX2 in BC is still unknown.
NUSAP1 (encodes nucleolar and spindle-associated protein 1), a nucleolar spindle-associated protein, has been reported that play a complicated role in cell division and mitotic progression, spindle formation, and stability [40]. It inhibits GBM cell growth both in vitro and vivo [41]. NUSAP1 was highly expressed in kinds of malignancies and correlated with poor prognosis in aggressive triple-negative BC [42].
Kinesin family member 20A (KIF20A) is believed to modulate microtubule dynamics [48], which could promote the tumorigenesis and progression of prostate cancer and glioma [49], particularly its biochemical recurrence and metastasis [48, 50]. Silencing KIF20A could induce prostate cancer cells to death [36]. The aberrantly activated Gli2-KIF20A axis is crucial for the growth of hepatocellular carcinoma and predicts poor prognosis in hepatocellular carcinoma [51].
MCAK(also known as KiF2C), a member of the motor protein-13 motor family, has been reported to undergo large conformational changes when it is converted from solution to microtubule-binding during its catalytic cycle [52]. The activity of MCAK is inhibited by Aurora B kinase through phosphorylation on multiple amino acids within its N-terminus [53, 54]. Previous studies reported that the high expression of KIF2C could serve as an independent marker of poor prognosis in several tumors, including glioma, colorectal cancer, and gastric cancer [55-57], but the roles in the BC reported less.
Ribonucleotide reductase M2 subunit (RRM2), a rate-limiting enzyme involved in DNA synthesis and damage repair, plays important roles in many cellular processes such as cell growth, invasiveness, migration and senescence et al [58]. RRM2 as a tumor driver is frequently overexpressed in various malignancies [59-61]. Others found that the expression level of RRM2 was correlated with invasion, cell differentiation, and metastasis in colorectal carcinoma [62]. Silencing RRM2 attenuated melanoma growth, which was consistent with the maintenance of senescence-associated cell-cycle arrest [63]. Also, it was correlated with lung cancer grade level [64].
Abnormal spindle-like microcephaly associated gene (ASPM), encodes a protein of 3477 amino acids with an NH2-terminal microtubule-binding domain, two calponin homology domains [65]. The function of APSM evidence has pointed out that it is an oncogene and the prognosis has been investigated in various cancers, such as epithelial ovarian cancer, gliomas, pancreatic and prostate cancer, and liver cancer, as well as BC, which devote to tumor progression and involved in poor prognosis [66-71].
Peroxisome proliferator-activated receptor gamma (PPARG) could induce cell cycle arrest, terminal differential, and anti-flammatory [72, 73], and induce G2/M cell cycle arrest by activating P38 in renal cancer and bladder cancer [74, 75]. Furthermore, PPARG induced down-regulated Wnt/beta-catenin pathway were observed and aberrant in many cancers [76], but sometimes PPARG is promoted in some tumors [72].