miR-93 and PTEN: Key regulators of doxorubicin-resistance and EMT in breast cancer

Abstract

Abstract. It is not well established whether miR-93 is involved in drug resistance and epithelial-mesenchymal transition (EMT) in breast cancer, and its underlying mechanism remains uncertain. In the present study, the expression differences of miR-93 between paired breast cancer tissues confirmed it is involved in the progression of breast cancer. Such a difference was also observed in doxorubicin-resistant and -sensitive cells. Overexpressed miR-93 in sensitive cells revealed increases in cellular proliferation and the expression levels of drug-resistant-related genes, and a decrease in sensitivity to doxorubicin. This demonstrated the relationship between miR-93 and breast cancer drug resistance. Simultaneously, EMT was confirmed in miR-93 overexpressing sensitive cells. This indicated the triadic relationship among miR-93, EMT and drug resistance in breast cancer. We applied the Dual-luciferase Reporter assay to expose the direct interaction between miR-93 and PTEN, which suggested that miR-93 contributes to inducing EMT and drug resistance of breast cancer cells by targeting PTEN.

WITHDRAWN: Identification of a novel lncRNA‑miRNA‑mRNA competing endogenous RNA network associated with prognosis of breast cancer

“…For example, Ye et al demonstrated that miR-429 inhibits breast cancer cell progression by targeting ZEB1 and CRKL[21]. A recent study has revealed that miR-93 contributes to inducing EMT and drug resistance of breast cancer cells by targeting PTEN[22]. miR-338p is also found to be downregulated in breast cancer and act as tumor inhibitor in breast cancer by targeting SOX4[23].…”

MiR-181c affects estrogen-dependent endometrial carcinoma cell growth by targeting PTEN

“…Estrogens regulate many functions, for example, female reproductive system, cardiovascular system, nervous system, bone excretory system and immune response, in human organism [24]. Estrogens play a major role in physiological changes or pathological changes, including endometrial carcinoma, breast cancer, ovarian cancer and other tumors, in women [9,25,26]. Estradiol (E2) is the main component of estrogen.…”

“…A recent study has suggested that PTEN deficiency or low expression is closely related to tumor progression and poor prognosis [6]. PTEN was cloned by the three research groups at the same time in 1979, which has a high frequency of deletions and mutations in multiple advanced and metastatic tumors including bladder cancer [7], non-small cell lung cancer [8] and breast cancer [9]. In addition, some studies also suggested that PTEN was closely associated to endometrial carcinoma, for example, Sakurada reported that introduction of wild-type PTEN by application of adenovirus-mediated gene transfer technique could induce cell apoptosis [10].…”

Micromanaging autophagy with microRNAs to drive cancer metastasis

“…Intriguingly, there exists a group of miRNAs that appear to block autophagy and yet promote EMT. These include oncogenic miR-21, miR-29a, miR-93, miR-214 and the miR-221/222 cluster that are highly expressed in cancer [ Figure 2] [62][63][64][65][66][67][68][69][70][71][72][73]87] . It seems counter-intuitive that successful distant organ/tissue invasion can be achieved for cancer cells without autophagy, but it remains plausible that the effects of these miRNAs might be context-dependent.…”

“…It seems counter-intuitive that successful distant organ/tissue invasion can be achieved for cancer cells without autophagy, but it remains plausible that the effects of these miRNAs might be context-dependent. For example, overexpression of miR-21 and miR-93 have been shown to induce metastasis by targeting PTEN [64,69] , which in turn may promote the blockade of autophagy via activating the PI3K-Akt-mTOR signaling cascade. Since one miRNA can target many different genes, the biological Activator [30] mTOR Activates ULK1 initiation Upregulated [30] Activator [30,31] miR-146a…”