miR-449a inhibits colorectal cancer progression by targeting SATB2

Xiaohua Sun, Sanhong Liu, Pengfei Chen, Da Fu, Yingyong Hou, Jin Hu, Zhi Liu, Yuhang Jiang, Xinwei Cao, Chunyan Cheng, Xi Chen, Yu Tao, Cuifeng Li, Yiming Hu, Zhanjie Liu, Yu Zhan, Jie Mao, Qi Wang, Yushui Ma, Xianling Cong & 4 others Ran Sun, Yufang Shi, Mingliang Wang, Xiaoren Zhang

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

miR-449a has been reported to act as a tumor suppressor in several cancers, however, it is controversial whether it inhibits tumor growth in colorectal cancer. The mechanisms underlying its expression and functions in colorectal cancers are still largely unknown. SATB2 is a sensitive and specific marker for CRC diagnosis. However, the mechanisms by which the expression and functions of SATB2 are regulated still remain to be clarified. We investigated the expression and functional significance of miR-449a and SATB2 and the mechanisms of their dysregulation in human CRC cells. miR-449a overexpression or SATB2 depletion inhibited tumor growth and promoted apoptosis in colorectal tumor cells in vitro and in xenograft mouse model, partially by downregulating SATB2. Expression of miR-449a was increased epigenetically via knocking down their targets, particularly SATB2. miR-449a was downregulated and STAB2 expression was upregulated in human CRCs. Their expressions were significantly associated with overall survival of CRC patients. Our findings demonstrate the existence of a miR-449a-SATB2 negative feedback loop that maintains low levels of miR-449a as well as high level of SATB2, thereby promoting CRC development.

Original languageEnglish (US)
Pages (from-to)100975-100988
Number of pages14
JournalOncotarget
Volume8
Issue number60
DOIs
StatePublished - Jan 1 2017

Fingerprint

Colorectal Neoplasms
Neoplasms
Down-Regulation
Growth
Heterografts
Apoptosis
Survival

All Science Journal Classification (ASJC) codes

  • Oncology

Keywords

  • Colorectal cancer
  • SATB2
  • Tumorigenesis
  • miR-449a

Cite this

Sun, X., Liu, S., Chen, P., Fu, D., Hou, Y., Hu, J., ... Zhang, X. (2017). miR-449a inhibits colorectal cancer progression by targeting SATB2. Oncotarget, 8(60), 100975-100988. https://doi.org/10.18632/oncotarget.10900
Sun, Xiaohua ; Liu, Sanhong ; Chen, Pengfei ; Fu, Da ; Hou, Yingyong ; Hu, Jin ; Liu, Zhi ; Jiang, Yuhang ; Cao, Xinwei ; Cheng, Chunyan ; Chen, Xi ; Tao, Yu ; Li, Cuifeng ; Hu, Yiming ; Liu, Zhanjie ; Zhan, Yu ; Mao, Jie ; Wang, Qi ; Ma, Yushui ; Cong, Xianling ; Sun, Ran ; Shi, Yufang ; Wang, Mingliang ; Zhang, Xiaoren. / miR-449a inhibits colorectal cancer progression by targeting SATB2. In: Oncotarget. 2017 ; Vol. 8, No. 60. pp. 100975-100988.
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abstract = "miR-449a has been reported to act as a tumor suppressor in several cancers, however, it is controversial whether it inhibits tumor growth in colorectal cancer. The mechanisms underlying its expression and functions in colorectal cancers are still largely unknown. SATB2 is a sensitive and specific marker for CRC diagnosis. However, the mechanisms by which the expression and functions of SATB2 are regulated still remain to be clarified. We investigated the expression and functional significance of miR-449a and SATB2 and the mechanisms of their dysregulation in human CRC cells. miR-449a overexpression or SATB2 depletion inhibited tumor growth and promoted apoptosis in colorectal tumor cells in vitro and in xenograft mouse model, partially by downregulating SATB2. Expression of miR-449a was increased epigenetically via knocking down their targets, particularly SATB2. miR-449a was downregulated and STAB2 expression was upregulated in human CRCs. Their expressions were significantly associated with overall survival of CRC patients. Our findings demonstrate the existence of a miR-449a-SATB2 negative feedback loop that maintains low levels of miR-449a as well as high level of SATB2, thereby promoting CRC development.",
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Sun, X, Liu, S, Chen, P, Fu, D, Hou, Y, Hu, J, Liu, Z, Jiang, Y, Cao, X, Cheng, C, Chen, X, Tao, Y, Li, C, Hu, Y, Liu, Z, Zhan, Y, Mao, J, Wang, Q, Ma, Y, Cong, X, Sun, R, Shi, Y, Wang, M & Zhang, X 2017, 'miR-449a inhibits colorectal cancer progression by targeting SATB2', Oncotarget, vol. 8, no. 60, pp. 100975-100988. https://doi.org/10.18632/oncotarget.10900

miR-449a inhibits colorectal cancer progression by targeting SATB2. / Sun, Xiaohua; Liu, Sanhong; Chen, Pengfei; Fu, Da; Hou, Yingyong; Hu, Jin; Liu, Zhi; Jiang, Yuhang; Cao, Xinwei; Cheng, Chunyan; Chen, Xi; Tao, Yu; Li, Cuifeng; Hu, Yiming; Liu, Zhanjie; Zhan, Yu; Mao, Jie; Wang, Qi; Ma, Yushui; Cong, Xianling; Sun, Ran; Shi, Yufang; Wang, Mingliang; Zhang, Xiaoren.

In: Oncotarget, Vol. 8, No. 60, 01.01.2017, p. 100975-100988.

Research output: Contribution to journalArticle

TY - JOUR

T1 - miR-449a inhibits colorectal cancer progression by targeting SATB2

AU - Sun, Xiaohua

AU - Liu, Sanhong

AU - Chen, Pengfei

AU - Fu, Da

AU - Hou, Yingyong

AU - Hu, Jin

AU - Liu, Zhi

AU - Jiang, Yuhang

AU - Cao, Xinwei

AU - Cheng, Chunyan

AU - Chen, Xi

AU - Tao, Yu

AU - Li, Cuifeng

AU - Hu, Yiming

AU - Liu, Zhanjie

AU - Zhan, Yu

AU - Mao, Jie

AU - Wang, Qi

AU - Ma, Yushui

AU - Cong, Xianling

AU - Sun, Ran

AU - Shi, Yufang

AU - Wang, Mingliang

AU - Zhang, Xiaoren

PY - 2017/1/1

Y1 - 2017/1/1

N2 - miR-449a has been reported to act as a tumor suppressor in several cancers, however, it is controversial whether it inhibits tumor growth in colorectal cancer. The mechanisms underlying its expression and functions in colorectal cancers are still largely unknown. SATB2 is a sensitive and specific marker for CRC diagnosis. However, the mechanisms by which the expression and functions of SATB2 are regulated still remain to be clarified. We investigated the expression and functional significance of miR-449a and SATB2 and the mechanisms of their dysregulation in human CRC cells. miR-449a overexpression or SATB2 depletion inhibited tumor growth and promoted apoptosis in colorectal tumor cells in vitro and in xenograft mouse model, partially by downregulating SATB2. Expression of miR-449a was increased epigenetically via knocking down their targets, particularly SATB2. miR-449a was downregulated and STAB2 expression was upregulated in human CRCs. Their expressions were significantly associated with overall survival of CRC patients. Our findings demonstrate the existence of a miR-449a-SATB2 negative feedback loop that maintains low levels of miR-449a as well as high level of SATB2, thereby promoting CRC development.

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KW - Colorectal cancer

KW - SATB2

KW - Tumorigenesis

KW - miR-449a

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Sun X, Liu S, Chen P, Fu D, Hou Y, Hu J et al. miR-449a inhibits colorectal cancer progression by targeting SATB2. Oncotarget. 2017 Jan 1;8(60):100975-100988. https://doi.org/10.18632/oncotarget.10900