Keqiang Zhang

ARL4C depletion suppresses the resistance of ovarian cancer to carboplatin by disrupting cholesterol transport and autophagy via notch-RBP-Jκ-H3K4Me3-OSBPL5

Increasing studies indicate that cholesterol plays an important role in drug resistance. ARL4C is implicated in the export and import of cholesterol, therefore this study aimed to explore the effect of ARL4C on the resistance of ovarian cancer (OVC) to Carboplatin. This study collected OVC tissue samples from patients who are sensitive or resistant to carboplatin, and established Carboplatin-resistant OVC cell lines, OVCAR3(R) and SKOV3(R) using OVCAR3 and SKOV3. High throughput sequencing was conducted to find genes that regulated by ARL4C. Cholesterol esterification was performed to evaluate the transport of cholesterol from Lysosome (LY) to Endoplasmic reticulum (ER). The fluorescence of LC3-GFP-mRFP was used to evaluate the function of autophagy flux. As indicated by PCR, western blot and Immunohistochemistry, ARL4C was increased in the Carboplatin-resistant OVC tissues and cells. Knockdown of ARL4C attenuated the resistance of OVCAR3(R) and SKOV3(R) to Carboplatin. By suppressing Notch signal, ARL4C knockdown inhibited the transcriptional function of RBP-Jκ and RBP-Jκ-induced H3K4Me3, which collectively reduced OSBPL5 expression. OSBPL5 deficiency inhibited the transport of cholesterol from LYs to ER, which led to the accumulation of cholesterol in LYs and the dysfunction of autophagy. In summary, ARL4C knockdown attenuated the resistance of OVC to Carboplatin by disrupting cholesterol transport and autophagy. This study revealed a promising target to attenuate the resistance of OVC to Carboplatin and elucidated the potential mechanism.

LncRNA LAMTOR5‐AS1 sponges miR‐210‐3p and regulates cervical cancer progression

AbstractAimCervical cancer has attracted increasing attention in recent years, and the incidence has shown a trend of younger age. Therefore, it is an effective method to regulate the progression of cervical cancer through new prognostic biomarkers. The purpose of this study was to evaluate the potential of lncRNA LAMTOR5‐AS1 (LAMTOR5‐AS1) as a prognostic biomarker and reveal its regulatory role in cervical cancer.MethodsA total of 120 patients with cervical cancer were selected as research subjects to verify the prognostic effect of LAMTOR5‐AS1 in a series of experiments. The expression of LAMTOR5‐AS1 in cervical cancer tissues and cells was determined by polymerase chain reaction assay. The proliferation, migration, and invasion ability of cervical cancer cells were evaluated by Cell Counting Kit‐8 (CCK‐8) and Transwell assay. Luciferase reporter gene detection was used to determine the mechanism of LAMTOR5‐AS1 targeting miR‐210‐3p, and to reflect the prognostic value of LAMTOR5‐AS1 according to statistical methods.ResultsLAMTOR5‐AS1 decreased in cervical cancer tissues, while miR‐210‐3p expression increased. In the study of cervical cancer cells, it was found that the LAMTOR5‐AS1 sponge miR‐210‐3p was associated with the malignant progression of cervical cancer. Overexpression of LAMTOR5‐AS1 could effectively inhibit the development of cervical cancer cells and might be chosen as a prognostic biomarker of cervical cancer.ConclusionsLAMTOR5‐AS1 sponges miR‐210‐3p and modulates the progression of cervical cancer, which predict the prognosis of cervical cancer patients.