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MicroRNA-451 regulates AMPK/mTORC1 signaling and fascin1 expression in HT-29 colorectal cancer.
Cell Signal. 2014 Jan; 26(1):102-9.CS

Abstract

The earlier studies have shown that Fascin1 (FSCN1), the actin bundling protein, is over-expressed in colorectal cancers, and is associated with cancer cell progression. Here, we aimed to understand the molecular mechanisms regulating FSCN1 expression by focusing on mammalian target of rapamycin (mTOR) signaling and its regulator microRNA-451. We found that microRNA-451 was over-expressed in multiple colorectal cancer tissues, and its expression was correlated with mTOR complex 1 (mTORC1) activity and FSCN1 expression. In cultured colorectal cancer HT-29 cells, knockdown of FSCN1 by RNAi inhibited cell migration and proliferation. Activation of mTORC1 was required for FSCN1 expression, HT-29 cell migration and proliferation, as RAD001 and rapamycin, two mTORC1 inhibitors, suppressed FSCN1 expression, HT-29 cell migration and proliferation. Meanwhile, forced activation of AMP-activated protein kinase (AMPK), the negative regulator of mTORC1, by its activators or by the genetic mutation, inhibited mTORC1 activation, FSCN1 expression, cell migration and proliferation. In HT-29 cells, we found that over-expression of microRNA-451 inhibited AMPK activation, causing mTORC1 over-activation and FSCN1 up-regulation, cells were with high migration ability and proliferation rate. Significantly, these effects by microRNA-451 were largely inhibited by mTORC1 inhibitors or the AMPK activator AICAR. On the other hand, knockdown of miRNA-451 by the treatment of HT-29 cells with miRNA-451 antagomir inhibited mTORC1 activation and FSCN1 expression. The proliferation and migration of HT-29 cells after miRNA-45 knockdown were also inhibited. Our results suggested that the over-expressed microRNA-451 in colon cancer cells might inhibit AMPK to activate mTORC1, which mediates FSCN1 expression and cancer cell progression.

Authors+Show Affiliations

Department of Medical Oncology, Kunshan First People's Hospital Affiliated to Jiangsu University, 91 Qianjin Road, Kunshan 215300, Jiangsu Province, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23899558

Citation

Chen, Min-Bin, et al. "MicroRNA-451 Regulates AMPK/mTORC1 Signaling and Fascin1 Expression in HT-29 Colorectal Cancer." Cellular Signalling, vol. 26, no. 1, 2014, pp. 102-9.
Chen MB, Wei MX, Han JY, et al. MicroRNA-451 regulates AMPK/mTORC1 signaling and fascin1 expression in HT-29 colorectal cancer. Cell Signal. 2014;26(1):102-9.
Chen, M. B., Wei, M. X., Han, J. Y., Wu, X. Y., Li, C., Wang, J., Shen, W., & Lu, P. H. (2014). MicroRNA-451 regulates AMPK/mTORC1 signaling and fascin1 expression in HT-29 colorectal cancer. Cellular Signalling, 26(1), 102-9. https://doi.org/10.1016/j.cellsig.2013.07.017
Chen MB, et al. MicroRNA-451 Regulates AMPK/mTORC1 Signaling and Fascin1 Expression in HT-29 Colorectal Cancer. Cell Signal. 2014;26(1):102-9. PubMed PMID: 23899558.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MicroRNA-451 regulates AMPK/mTORC1 signaling and fascin1 expression in HT-29 colorectal cancer. AU - Chen,Min-Bin, AU - Wei,Mu-Xin, AU - Han,Jun-Yi, AU - Wu,Xiao-Yang, AU - Li,Chen, AU - Wang,Jian, AU - Shen,Wei, AU - Lu,Pei-Hua, Y1 - 2013/07/27/ PY - 2013/03/22/received PY - 2013/06/26/revised PY - 2013/07/19/accepted PY - 2013/8/1/entrez PY - 2013/8/1/pubmed PY - 2014/6/26/medline KW - 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside KW - ACC KW - AICAR KW - AMP-activated protein kinase KW - AMPK KW - Acetyl-CoA Carboxylase KW - CAB39 KW - Colorectal cancer KW - FSCN1 KW - Fascin1 KW - MicroRNA KW - RNA interference KW - RNAi KW - Raptor KW - S6K1 KW - TSC2 KW - Tuberous sclerosis protein 2 and untranslated regions (UTRs) KW - calcium-binding protein 39 KW - fascin1, mammalian target of rapamycin (mTOR) KW - mTOR complex 1 KW - mTOR signaling KW - mTORC1 KW - regulatory associated protein of mTOR KW - ribosomal p70 S6 kinase SP - 102 EP - 9 JF - Cellular signalling JO - Cell Signal VL - 26 IS - 1 N2 - The earlier studies have shown that Fascin1 (FSCN1), the actin bundling protein, is over-expressed in colorectal cancers, and is associated with cancer cell progression. Here, we aimed to understand the molecular mechanisms regulating FSCN1 expression by focusing on mammalian target of rapamycin (mTOR) signaling and its regulator microRNA-451. We found that microRNA-451 was over-expressed in multiple colorectal cancer tissues, and its expression was correlated with mTOR complex 1 (mTORC1) activity and FSCN1 expression. In cultured colorectal cancer HT-29 cells, knockdown of FSCN1 by RNAi inhibited cell migration and proliferation. Activation of mTORC1 was required for FSCN1 expression, HT-29 cell migration and proliferation, as RAD001 and rapamycin, two mTORC1 inhibitors, suppressed FSCN1 expression, HT-29 cell migration and proliferation. Meanwhile, forced activation of AMP-activated protein kinase (AMPK), the negative regulator of mTORC1, by its activators or by the genetic mutation, inhibited mTORC1 activation, FSCN1 expression, cell migration and proliferation. In HT-29 cells, we found that over-expression of microRNA-451 inhibited AMPK activation, causing mTORC1 over-activation and FSCN1 up-regulation, cells were with high migration ability and proliferation rate. Significantly, these effects by microRNA-451 were largely inhibited by mTORC1 inhibitors or the AMPK activator AICAR. On the other hand, knockdown of miRNA-451 by the treatment of HT-29 cells with miRNA-451 antagomir inhibited mTORC1 activation and FSCN1 expression. The proliferation and migration of HT-29 cells after miRNA-45 knockdown were also inhibited. Our results suggested that the over-expressed microRNA-451 in colon cancer cells might inhibit AMPK to activate mTORC1, which mediates FSCN1 expression and cancer cell progression. SN - 1873-3913 UR - https://www.unboundmedicine.com/medline/citation/23899558/MicroRNA_451_regulates_AMPK/mTORC1_signaling_and_fascin1_expression_in_HT_29_colorectal_cancer_ DB - PRIME DP - Unbound Medicine ER -