Juan Zhao

MicroRNA‐367‐3p overexpression represses the proliferation and invasion of cervical cancer cells through downregulation of SPAG5‐mediated Wnt/β‐catenin signalling

AbstractMicroRNA‐367‐3p (miR‐367‐3p) has been previously reported as a cancer‐related miRNA that is dysregulated in various cancer types and functions either as an oncogenic or as tumour suppressive miRNA. However, whether miR‐367‐3p is dysregulated in cervical cancer and, further, whether it contributes to the development and progression of the disease remains unknown. Here, our results demonstrated that miR‐367‐3p expression was markedly decreased in both cervical cancer tissues and cell lines compared with corresponding controls. In vitro experiments revealed that miR‐367‐3p overexpression repressed the proliferation and invasion of cervical cancer cells. Notably, sperm‐associated antigen 5 (SPAG5) was identified as a target gene of miR‐367‐3p. Moreover, decreased expression of miR‐367‐3p was correlated with high expression of SPAG5 in cervical cancer tissue specimens. SPAG5 inhibition or miR‐367‐3p overexpression significantly downregulated Wnt/β‐catenin signalling in cervical cancer cells. However, the antitumour effect mediated by miR‐367‐3p overexpression was partially reversed by SPAG5 overexpression. Overall, these findings demonstrate that miR‐367‐3p overexpression restricts the proliferation and invasion of cervical cancer cells through targeting SPAG5 to downregulate Wnt/β‐catenin signalling, suggesting a mechanism for the tumour suppressive function of miR‐367‐3p in cervical cancer. Our study highlights the involvement of miR‐367‐3p/SPAG5/Wnt/β‐catenin signalling axis in regulating the malignant progression of cervical cancer.

Antitumor activity of pachymic acid in cervical cancer through inducing endoplasmic reticulum stress, mitochondrial dysfunction, and activating the AMPK pathway

AbstractPachymic acid has various pharmacological effects, including anti‐inflammatory, antioxidant, immunomodulatory, and antitumor. However, the role of pachymic acid in cervical cancer remains unclear. So, we investigated the effects of pachymic acid in cervical cancer and elucidated the underlying mechanisms. We treated HeLa cells and normal cervical epithelial cells (HUCECs) with pachymic acid (0, 10, 20, 40, 80, or 160 μM) for 72 h, and found the cell activity was decreased in cells treated with 160 μM pachymic acid for 48 h or 80 μM pachymic acid for 72 h, while HUCECs viability without effect. Next, we observed that endoplasmic reticulum (ER) related gene expression, mitochondrial membrane potential (MMP) changes, ATP depletion, reactive oxygen species (ROS) generation and apoptosis were increased. Moreover, we observed that cytochrome C (Cytc) expression was increased and apoptosis‐inducing factor (AIF) was decreased in the cytoplasm of pachymic acid‐treated HeLa cells. Tauroursodeoxycholic acid (TUDCA) of ER stress inhibitor reversed the effects of pachymic acid on HeLa cells. Phosphorylation of AMPK and acetyl‐CoA carboxylase (ACC) of the AMPK pathway key protein was upregulated in pachymic acid‐induced HeLa cells. Finally, we subcutaneously implanted HeLa cells into female nude mice and treated them with pachymic acid (50 mg/kg) for 3 weeks (5 days/week), and observed in pachymic acid induced xenograft mice, tumor growth was suppressed, cell apoptosis, ER‐related gene expression, and ROS levels in tumor tissues were increased. Therefore, these findings demonstrated that pachymic acid plays an anti‐tumor activity in cervical cancer through inducing ER stress, mitochondrial dysfunction, and activating the AMPK pathway.