MicroRNA-520a-5p displays a therapeutic effect upon chronic myelogenous leukemia cells by targeting STAT3 and enhances the anticarcinogenic role of capsaicin

Abstract

Aberrant expression profiles of microRNAs (miRNAs) have been previously demonstrated for having essential roles in a wide range of cancer types including leukemia. Antiproliferative or proapoptotic effects of capsaicin have been reported in several cancers. We aimed to study miRNAs involved in the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway in chronic myeloid leukemia cell model and the effects of the capsaicin treatment on cell proliferation and miRNA regulation. miR-520a-5p expression was extremely downregulated in capsaicin-treated cells. Repressing the level of miR-520a-5p by transient transfection with specific miRNA inhibitor oligonucleotides resulted in induced inhibition of proliferation in leukemic cells. According to bioinformatics analysis, STAT3 messenger RNA was predicted as a putative miR-520a-5p target; which was confirmed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and Western blot analysis. Cell proliferation inhibition was enhanced upon knockdown of STAT3 by RNA interference applications, but when miR-520a-5p inhibitor was additionally transfected onto STAT3 silenced cells, cell viability was dramatically decreased in leukemia cells. Finally, we observed the effects of capsaicin following miR-520a-5p inhibitor transfection upon cell proliferation, apoptosis, and STAT3 expression levels. We determined that, downregulation of miR-520a-5p affected the proliferation inhibition enhanced by capsaicin and reduced STAT3 mRNA and protein expression levels and increased apoptotic cell number. In summary, miR-520a-5p displays a therapeutic effect by targeting STAT3 and impacting the anticancer effects of capsaicin; whereas capsaicin, potentially through the miR-520a-5p/STAT3 interaction, induces apoptosis and inhibits K562 leukemic cell proliferation with need of further investigation.

Capsaicin causes inactivation and degradation of the androgen receptor by inducing the restoration of miR-449a in prostate cancer

“…signaling. Previous research has confirmed that capsaicin regulates the expression of various miRNAs, such as miR-34a (16) and miR-520-5p (17). Firstly, we detected miR-449a expression in several AR-positive PCa cell lines.…”

“…Chakraborty et al found that increased miR-34a expression by capsaicin decreased the survival advantage and enhanced Bax-dependent apoptosis in non-small cell lung cancers (16). Kaymaz et al proved that capsaicin suppressed the growth of chronic myelogenous leukemia cells by decreasing expression of miR-520a-5p which was shown as a probable oncogene (17). They also found that inhibition of miR520-5p enhanced the antitumor effect of capsaicin.…”

Overexpression of miR‑574‑3p suppresses proliferation and induces apoptosis of chronic myeloid leukemia cells via targeting IL6/JAK/STAT3 pathway

“…JAK/STAT3 pathway is shown to be a key mechanism to mediate cryptotanshinone-induced apoptosis of CML K562 cells (27). Besides, capsaicin can induce apoptosis and inhibit proliferation of K562 leukemic cells through affecting miR-520a-5p/STAT3 interaction (28). Bortezomib can induce apoptosis of K562 leukemic cells by interacting with JAK/STAT pathway (29).…”

Capsaicin enhances the antitumor activity of sorafenib in hepatocellular carcinoma cells and mouse xenograft tumors through increased ERK signaling

“…Capsaicin has attracted considerable attention because of its chemoprotective properties against certain carcinogens and mutagens [13] . In addition, capsaicin has been reported to induce cell apoptosis in several tumor types, such as myeloid leukemia, colon cancer, and HCC [14][15][16][17] . The www.chinaphar.com Zhang SS et al Acta Pharmacologica Sinica mechanisms whereby capsaicin induces cancer cell apoptosis were reported to be either dependent or independent on the transient receptor potential vanilloid 1 (TRPV1) channel that serves as a direct target of capsaicin [18,19] .…”