Downregulated miR‑21 mediates matrine‑induced apoptosis via the PTEN/Akt signaling pathway in FTC‑133 human follicular thyroid cancer cells

Abstract

Matrine is an alkaloid extracted from the leguminous plant Sophora flavescens. Matrine has clinical effects in the treatment of tumors, including those in lung cancer, nasopharyngeal cancer and liver cancer. However, the effect of matrine on follicular thyroid cancer has not been reported. The aim of the present study was to investigate the effect of matrine on follicular thyroid cancer and its potential mechanism. FTC-133 follicular thyroid cancer cells were treated with different concentrations of matrine, and an MTT assay showed that matrine inhibited the growth of FTC-133 cells in a dose- and time-dependent manner with an IC50 value of 154.8 µM. Cell apoptosis was analyzed by flow cytometry and the results showed that matrine effectively induced the apoptosis of FTC-133 cells. The expression level of microRNA (miR)-21 was analyzed by reverse transcription-quantitative PCR (RT-qPCR) analysis, and the mRNA and protein expression levels of PTEN, Akt and phosphorylated (p)-Akt were detected by RT-qPCR analysis and western blotting, respectively. The expression of miR-21 was significantly downregulated, PTEN was upregulated at the mRNA and protein expression levels, and p-Akt was downregulated in the FTC-133 cells. The effects of miR-21 mimics and miR-21 inhibitor on the expression of miR-21, PTEN and Akt in FTC-133 cells, and the effect of miR-21 mimics/matrine on the expression of PTEN were also investigated. The results of the present study suggested that matrine inhibited the growth and induced apoptosis of FTC-133 cells via the miR-21/PTEN/Akt signaling pathway.

mir-21 is associated with inactive low molecular weight Argonaute complexes in thyroid cancer cell lines

“…It is frequently deregulated in tumors, including thyroid, and is often described as an oncogenic miRNA or oncomiR [41] [42]. Numerous studies have demonstrated that aberrantly high levels of miR-21 promote tumor growth by negatively regulating the expression of tumor suppressor genes such as PTEN [43] [44]. Additionally, tumors may become reliant on miR-21 in a phenomenon known as oncogene addiction, and down-regulation of miR-21 often results in tumor regression [45] [46].…”

“…Total RNA and small RNA quality control was by Fragment Analyzer (Agilent version# 1.1.0.11). qPCR was performed with 2 µL RNA input from each fraction, or from pooled fractions HMW-RISC (15)(16), MMW-RISC (17-26), LMW-RISC (27)(28)(29)(30)(31)(32)(33)(34)(35), and RISC-Poor (36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47) using TaqMan microRNA Reverse transcription kit (ABI 4366597 Lot#00636931), TaqMan miRNA stem-loop RT primers/qPCR primer probe sets (ABI 4427975) (cel-miR-39 ID# 000200 Lot#P180110-003B10, miR-16 ID# 000391 Lot#P171018-000H05, U6 ID# 001937 Lot#P170729-001405), TaqMan Universal Master Mix II, no UNG (ABI 4440040 Lot#1802074), as described in manufacturer's protocol, on a CFX96 Real-time System (Bio-Rad). For each RNA fraction, miR-16 and U6 were normalized to cel-miR-39, then to fraction 14 using the 2 -ΔΔCT method.…”

Anti-Tumor Mechanisms Associated With Regulation of Non-Coding RNA by Active Ingredients of Chinese Medicine: A Review

“…PTEN is a classical anti-oncogene, the inhibition of PTEN is key for cell apoptosis, mainly relying on the phosphorylation and dephosphorylation of Akt. In FTC-133 human follicular thyroid cells, the alkaloid Chinese medicine active ingredient matrine is induced by upregulating the PTEN/Akt signaling pathway via the downregulating miR-21 ( 39 ) it induces apoptosis of TPC-1 human thyroid cancer cells ( 40 ). Similarly, the reverse quantitative polymerase chain reaction of an extract of Magnolia officinalis revealed that magnolol could induce abnormal expression of miRNA in human osteosarcoma cells, with miR-21 showing a very strong ability to downregulate mRNAs.…”

Regulation of microRNA‐21 expression by natural products in cancer

“…Matrine induced apoptosis in TPC-1 human thyroid cancer cells, FTC-133 human follicular thyroid cancer, and MCF-7 breast cancer through downregulation of miR-21 and subsequent upregulation of PTEN and decreased phosphorylation of Akt signaling pathway (L. Q. Q. Li et al, 2019;Zhao, Zhang, & Cui, 2018).…”

“…It was found that inhibition of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase led to reduced miR‐21 expression and metastasis in lung cancer both in‐vitro and in‐vivo (S. Yan et al, 2015). Matrine induced apoptosis in TPC‐1 human thyroid cancer cells, FTC‐133 human follicular thyroid cancer, and MCF‐7 breast cancer through downregulation of miR‐21 and subsequent upregulation of PTEN and decreased phosphorylation of Akt signaling pathway (L. Q. Li et al, 2012; Q. Li et al, 2019; Zhao, Zhang, & Cui, 2018).…”