COL14A1 promotes self-renewal of human liver cancer stem cells through activation of ERK signaling
作者单位：Shanghai Fourth People’s Hospital 海军军医大学第一附属医院(上海长海医院)
会议名称：《2021年中国肿瘤标志物学术大会暨第十五届肿瘤标志物青年科学家论坛》
会议日期：2021年
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
关 键 词：COL14A1 ERK signaling hepatocellular carcinoma miR-7108-3p liver cancer stem cells
摘 要：Objective: Liver cancer stem cells(CSCs) are the culprits of hepatocellular carcinoma metastasis and recurrence. Only by eliminating tumor stem cells can malignant tumors be fundamentally cured. This study aimed to identify the role and underlying mechanism of aberrant Collagen Type XIV Alpha 1 Chain(COL14 A1) overexpression in liver CSCs, and improve understanding of the molecular basis of hepatocellular carcinoma metastasis and ***: First, quantitative real-time polymerase chain reaction was used to confirm aberrant highexpression of COL14 A1 in liver CSCs. Next, interference experiments were performed to determine the key role of COL14 A1. To explore the mechanism of COL14 A1 overexpression in liver CSCs,putative microRNA(miRNAs) targeting COL14 A1 were analyzed using the miRTarBase ***, quantitative real-time polymerase chain reaction, western blotting, and luciferase reporter assays were performed to verify the interaction between miR-7108-3 p and COL14 A1. Lastly, key target proteins of the COL14 A1-extracellular-regulated signal kinase(ERK) signaling pathway were identified through western blotting analysis. This study was approved by the Ethics Committee of Shanghai Fourth People’s Hospital, Tongji University School of Medicine, China(approval No.2019 tjdx17) on February 21, ***: COL14 A1 is abnormally highly expressed in liver CSCs, which is necessary for liver CSCs to maintain their self-renewal capability. Mechanistically, COL14 A1 is post-transcriptionally regulated by miR-7108-3 p in a negative manner. Low expression of miR-7108-3 p increased translation of COL14 A1, which subsequently activated ERK signaling, ultimately maintaining the self-renewal and stem cell-like properties of liver ***: COL14 A1, which is negatively regulated by miR-7108-3 p, was found to play a crucial role in maintaining the self-renewal and stem cell-like properties of liver CSCs through activation of ERK signaling.
