MiR-142-3p enhances chemosensitivity of breast cancer cells and inhibits autophagy by targeting HMGB1

MiR-142-3p has been reported to act as a tumor suppressor in breast cancer. However, the regulatory effect of miR-142-3p on drug resistance of breast cancer cells and its underlying mechanism remain unknown. Here, we found that miR-142-3p was significantly downregulated in the doxorubicin (DOX)-resistant MCF-7 cell line (MCF-7/DOX). MiR-142-3p overexpression increased DOX sensitivity and enhanced DOX-induced apoptosis in breast cancer cells. High-mobility group box 1 (HMGB1) is a direct functional target of miR-142-3p in breast cancer cells and miR-142-3p negatively regulated HMGB1 expression. Moreover, overexpression of HMGB1 dramatically reversed the promotion of apoptosis and inhibition of autophagy mediated by miR-142-3p up-regulation. In conclusion, miR-142-3p overexpression may inhibit autophagy and promote the drug sensitivity of breast cancer cells to DOX by targeting HMGB1. The miR-142-3p/HMGB1 axis might be a novel target to regulate the drug resistance of breast cancer patients.

Human Corneal Tissue Model for Nociceptive Assessments.

New in vitro tissue models to mimic in vivo conditions are needed to provide insight into mechanisms involved in peripheral pain responses, potential therapeutic strategies to address these responses, and to replace animal models for such indications. For example, the rabbit cornea Draize test has become the standard method used for decades to screen ophthalmic drug and consumer product toxicity. In vitro tissue models with functional innervation have the potential to replace in vivo animal testing and provide sophisticated bench tools to study ocular nociception and its amelioration. Herein, full thickness, innervated, 3D human corneal tissues are grown under physiologically relevant culture conditions to study nociceptive-related responses, by mimicking ocular environmental cues, including intraocular pressure (IOP) and tear flow (TF). Capsaicin, a chili pepper-derived irritant known to cause a burning sensation in mammalian tissues is utilized as a nociceptive stimulant to induce pain, while subsequent serum treatment is used to mimic healing. Pain mediators released upon capsaicin stimulation and cell regrowth after serum treatment are characterized to assess ocular responses in this new, innervated, human corneal tissue system for comparison of outcomes to established animal and related responses.