» Articles » PMID: 19513126

Upregulation of MiR-23a-27a-24-2 Cluster Induces Caspase-dependent and -independent Apoptosis in Human Embryonic Kidney Cells

Overview
Journal PLoS One
Date 2009 Jun 11
PMID 19513126
Citations 73
Authors
Affiliations
Soon will be listed here.
Abstract

miRNAs have emerged as important players in the regulation of gene expression and their deregulation is a common feature in a variety of diseases, especially cancer. Currently, many efforts are focused on studying miRNA expression patterns, as well as miRNA target validation. Here, we show that the over expression of miR-23a approximately 27a approximately 24-2 cluster in HEK293T cells induces apoptosis by caspase-dependent as well as caspase-independent pathway as proved by the annexin assay, caspase activation, release of cytochrome-c and AIF (apoptosis inducing factor) from mitochondria. Furthermore, the over expressed cluster modulates the expression of a number of genes involved in apoptosis including FADD (Fas Associated protein with Death Domain). Bioinformatically, FADD is predicted to be the target of hsa-miR-27a and interestingly, FADD protein was found to be up regulated consistent with very less expression of hsa-miR-27a in HEK293T cells. This effect was direct, as hsa-miR-27a negatively regulated the expression of FADD 3'UTR based reporter construct. Moreover, we also showed that over expression of miR-23a approximately 27a approximately 24-2 sensitized HEK293T cells to TNF-alpha cytotoxicity. Taken together, our study demonstrates that enhanced TNF-alpha induced apoptosis in HEK293T cells by over expression of miR-23a approximately 27a approximately 24-2 cluster provides new insights in the development of novel therapeutics for cancer.

Citing Articles

RCOR1 is targeted by miR-23b-3p to modulate growth, colony formation, migration, and invasion of prostate cancer cells.

Liu C, Dong Z, Li M, Bai G, Zhao Z Int J Clin Exp Pathol. 2024; 17(2):29-38.

PMID: 38455506 PMC: 10915288.


Quercetin's Dual Mode of Action to Counteract the Sp1-miR-27a Axis in Colorectal Cancer Cells.

Fosso E, Leo M, Muccillo L, Mandrone V, Di Meo M, Molinario A Antioxidants (Basel). 2023; 12(8).

PMID: 37627542 PMC: 10451631. DOI: 10.3390/antiox12081547.


The Role of microRNA-23a-3p in the Progression of Human Aging Process by Targeting FOXO3a.

Wang S, Sun Y, Yao L, Xing Y, Yang H, Ma Q Mol Biotechnol. 2023; 66(2):277-287.

PMID: 37087718 PMC: 10803409. DOI: 10.1007/s12033-023-00746-7.


The Host Non-Coding RNA Response to Alphavirus Infection.

Behnia M, Bradfute S Viruses. 2023; 15(2).

PMID: 36851776 PMC: 9967650. DOI: 10.3390/v15020562.


Promising Biomarkers in Head and Neck Cancer: The Most Clinically Important miRNAs.

Thomaidou A, Batsaki P, Adamaki M, Goulielmaki M, Baxevanis C, Zoumpourlis V Int J Mol Sci. 2022; 23(15).

PMID: 35897831 PMC: 9367895. DOI: 10.3390/ijms23158257.


References
1.
Newton K, Harris A, Strasser A . FADD/MORT1 regulates the pre-TCR checkpoint and can function as a tumour suppressor. EMBO J. 2000; 19(5):931-41. PMC: 305633. DOI: 10.1093/emboj/19.5.931. View

2.
Rehmsmeier M, Steffen P, Hochsmann M, Giegerich R . Fast and effective prediction of microRNA/target duplexes. RNA. 2004; 10(10):1507-17. PMC: 1370637. DOI: 10.1261/rna.5248604. View

3.
Goel A, Prasad A, Parmar V, Ghosh B, Saini N . 7,8-Dihydroxy-4-methylcoumarin induces apoptosis of human lung adenocarcinoma cells by ROS-independent mitochondrial pathway through partial inhibition of ERK/MAPK signaling. FEBS Lett. 2007; 581(13):2447-54. DOI: 10.1016/j.febslet.2007.04.052. View

4.
Su Y, Chang H, Shyue S, Hsu S . Emodin induces apoptosis in human lung adenocarcinoma cells through a reactive oxygen species-dependent mitochondrial signaling pathway. Biochem Pharmacol. 2005; 70(2):229-41. DOI: 10.1016/j.bcp.2005.04.026. View

5.
Volinia S, Calin G, Liu C, Ambs S, Cimmino A, Petrocca F . A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A. 2006; 103(7):2257-61. PMC: 1413718. DOI: 10.1073/pnas.0510565103. View