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ITPKA induces cell senescence, inhibits ovarian cancer tumorigenesis and can be downregulated by miR-203.

ABSTRACT: Overcoming senescence is a feature of ovarian cancer cells; however, the mechanisms underlying senescence regulation in ovarian cancer cells remain largely unknown. In this study, we found that ITPKA was downregulated in ovarian cancer samples, and the lower expression correlated with poor survival. Overexpression of ITPKA inhibited the anchorage-independent growth of ovarian cancer cells and induced senescence. However, knockdown of ITPKA promoted the anchorage-independent growth of ovarian cancer cells and inhibited senescence. Mechanistically, ITPKA was found to interact with MDM2, which stabilized P53, an essential regulator of senescence. Moreover, ITPKA was negatively regulated by miR-203, a microRNA that has been previously reported to be upregulated in ovarian cancer. Taken together, the results of this study demonstrated the tumor suppressive roles of ITPKA in ovarian cancer and provided a good explanation for the oncogenic roles of miR-203.

SUBMITTER: Shaosheng W

PROVIDER: S-EPMC8109125 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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ITPKA induces cell senescence, inhibits ovarian cancer tumorigenesis and can be downregulated by miR-203.

Shaosheng Wang W Shaochuang Wang W Lichun Fan F Na Xie X Xiaohong Zhao Z

Aging 20210420 8

Overcoming senescence is a feature of ovarian cancer cells; however, the mechanisms underlying senescence regulation in ovarian cancer cells remain largely unknown. In this study, we found that ITPKA was downregulated in ovarian cancer samples, and the lower expression correlated with poor survival. Overexpression of ITPKA inhibited the anchorage-independent growth of ovarian cancer cells and induced senescence. However, knockdown of ITPKA promoted the anchorage-independent growth of ovarian can ...[more]

PMID: 33879633

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