Appropriate cell cycle progression is orchestrated by a series of molecular events in which the ubiquitin/proteasome system is strongly associated with the cell cycle oscillation machinery [
1,
2]. Therefore, dysfunction of this system often leads to chromosomal instability and eventually results in the initiation of diseases, such as malignant tumors [
5,
6]. The ubiquitin/proteasome system includes ubiquitin activating enzyme (E1), ubiquitin conjugating enzyme (E2), and E3 ligase. Two major E3 ligases, SCF and APC, are critical for governing mitosis or G1/S progression [
5‐
7]. Loss of function of the SCF or APC pathways is involved in the initiation or progression of human cancer [
24‐
26]. Previous work also provides evidence that E2 proteins play an important role in regulating cell cycle progression. Indeed, recent studies demonstrate that UbcH10 promotes the dissociation of Mad2 from Cdc20, a crucial step in the metaphase to anaphase transition in which important molecules are involved in the organization of appropriate spindle assembly checkpoints [
9,
10]. The function of the spindle assembly checkpoint is to ensure the proper separation of duplicated daughter genomes during mitosis, and the dysfunction of this system often results in aneuploidy or tetraploidy [
25,
26]. In fact, abnormal levels of Mad1, Mad2, BubR1, and aurora A are observed in prostate, stomach, and lung cancers [
13‐
15,
27]. Our results using cultured cells, as well as the epigenetic analysis, further confirms that dysfunction of the spindle assembly checkpoint could potentially induce the initiation or progression of cancer.
Abnormal levels of UbcH10 promote aberrant cell cycle progression and are potentially associated with tumor progression [
18‐
20,
27]. Cell culture studies have indicated the potential oncogenic role of UbcH10 [
18,
27]. Given the correlation between mitotic machinery dysfunction and chromosomal instability, the association between UbcH10 and mitotic regulation further implicates the involvement of UbcH10 in tumorigenesis [
18,
20,
27]. Our results suggest that abnormal levels of UbcH10 increase oncogenic potential and accelerate cellular proliferation. Furthermore, UbcH10 overexpression or knockdown induced significant changes in the cell cycle profile and the properties of oncogenic growth in colon cancer cells, which is consistent with the prior observation that UbcH10 participates in the progression of cancer.
Clinicopathological analysis confirms the oncogenic role of UbcH10
The results of our examination of the association between UbcH10, lymph-node metastasis, and histological grade of colon cancers provoked the hypothesis that UbcH10 could promote tumor growth via abrogation of the spindle assembly checkpoint [
18,
27]. Our analysis indicated that UbcH10-negative colon cancers were associated with a low histological grade and the loss of aggressive cancer behavior. Thus, this potentially links UbcH10 activity to the biological characteristics of tumor. Indeed, previous results of large-scale genetic screening studies have revealed that UbcH10 is one of the candidate molecules related to aggressive behavior of the tumors [
28‐
33]. Therefore, our clinicopathological assessment of UbcH10 is compatible with prior epigenetic and biological studies that have implicated UbcH10 as a predictor of the biological characteristics of cancer. Furthermore, lower levels of p31comet, another molecule that induces the metaphase to anaphase transition, also acts as a potential prognostic marker in cancer [
34,
35]. Moreover, Usp44 inhibits Cdc20 degradation and counteracts UbcH10 to decelerate the metaphase to anaphase transition [
36]. Therefore, a balance between UbcH10 and Usp44 could determine the appropriate timing of sister chromatid separation and further explain the significance of UbcH10 in cancer [
36].
Our study had limitation. We could not adequately address the phenomenon that overexpression of UbcH10 induced cellular proliferation while contradictory decreased the population of mitosis. However, our results were consistent with the results of previous literatures, which may even be considered as strength of the present study. Currently, role of UbcH10 is suggested to be only at the end of G1-phase, being inconsistent with both in the spindle checkpoint and inactivation of the APC/C [
37]. Their suggestion would be the potential clue to explain the contradictory phenomenon, and further investigation is required to unveil the controversial point of UbcH10.