MiR-140-3p/usp36 axis mediates ubiquitination to regulate PKM2 and suppressed the malignant biological behavior of breast cancer through Warburg effect

Abstract

ABSTRACT Breast cancer is a phenomenon in which breast epithelial cells proliferate out of control under the action of various carcinogenic factors. However, the role of USP36 in breast cancer is unknown. We analyzed the expression of USP36 in breast cancer and its association with poor prognosis in breast cancer patients. The effect of USP36 on malignant biological behavior of breast cancer was verified by cell functional experiments. The upstream regulatory mechanism of USP36 was analyzed by Western blot and quantitative RT-qPCR. The influence of USP36 on the Warburg effect of breast cancer was analyzed by detecting the metabolism of cellular energy substances. We found that USP36 is highly expressed in breast tumor tissues and breast cancer cell lines. High expression of USP36 predicts poor prognosis in patients with breast cancer. Effectively reducing the expression of USP36 can significantly inhibit the proliferation, invasion and migration of breast cancer cells, and promote the apoptosis of breast cancer cells. Meanwhile, inhibiting the expression of USP36 can significantly inhibit the production of ATP, lactate, pyruvate and glucose uptake in breast cancer cells. miR-140-3p is an upstream regulator of USP36, which can partially reverse the regulatory effect of USP36 on breast cancer cells. Importantly, USP36 regulates the expression of PKM2 through ubiquitination, which plays a role in regulating the Warburg effect. We confirmed that miR-140-3p regulates the expression of USP36, which mediates ubiquitination and regulates the expression of PKM2, and regulates the malignant biological behavior of breast cancer through the energy metabolism process.