Post-transcriptional repression of circadian component clock regulates cancer-stemness in murine breast cancer cells

Takashi Ogino, Naoya Matsunaga, Takahiro Tanaka, Tomohito Tanihara, Hideki Terajima, Hikari Yoshitane, Yoshitaka Fukada, Akito Tsuruta, Satoru Koyanagi, Shigehiro Ohdo

研究成果: Contribution to journalArticle査読

抄録

Disruption of the circadian clock machinery in cancer cells is implicated in tumor malignancy. Studies on cancer therapy reveal the presence of heterogeneous cells, including breast cancer stem-like cells (BCSCs), in breast tumors. BCSCs are often characterized by high aldehyde dehydrogenase (ALDH) activity, associated with the malignancy of cancers. In this study, we demonstrated the negative regulation of ALDH activity by the major circadian component CLOCK in murine breast cancer 4T1 cells. The expression of CLOCK was repressed in high-ALDH-activity 4T1, and enhancement of CLOCK expression abrogated their stemness properties, such as tumorigenicity and invasive potential. Furthermore, reduced expression of CLOCK in high-ALDHactivity 4T1 was post-transcriptionally regulated by microRNA: miR-182. Knockout of miR-182 restored the expression of CLOCK, resulted in preventing tumor growth. Our findings suggest that increased expression of CLOCK in BCSCs by targeting post-transcriptional regulation overcame stemness-related malignancy and may be a novel strategy for breast cancer treatments.

本文言語英語
論文番号e66155
ジャーナルeLife
10
DOI
出版ステータス出版済み - 2021

All Science Journal Classification (ASJC) codes

  • 神経科学(全般)
  • 生化学、遺伝学、分子生物学(全般)
  • 免疫学および微生物学(全般)

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