LncRNA MALAT1 facilitates ovarian cancer progression through promoting chemoresistance and invasiveness in the tumor microenvironment
Journal
International Journal of Molecular Sciences
Journal Volume
22
Journal Issue
19
Pages
10201
Date Issued
2021
Author(s)
Abstract
Upregulation of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1, also known as nuclear-enriched abundant transcript 2 (NEAT2) or LINC00047) was found in various solid tumors, including epithelial ovarian cancer (EOC). MALAT1 is a long noncoding (lnc)RNA that regulates many functional signaling pathways, including tumorigenesis. Herein, we observed the consistent upregulation of MALAT1 in MYST4-overexpressing cell lines, while MALAT1 was frequently found to be upregulated in various types of clinical carcinoma tissues, especially EOC. To further investigate the lncRNA MALAT1 in EOC progression, the transduced overexpression of MALAT1 in EOC cell lines and cancer-associated fibroblasts (CAFs) was employed. We found that MALAT1 overexpression in EOC cell lines significantly increased drug resistance, cell migration, and invasion. Furthermore, the concomitant overexpression of MALAT1 in EOC cells and CAFs dramatically increased EOC cell invasion. Accordingly, a mechanistic investigation of MALAT1 overexpression in EOC cells showed that expressions of the cytokines interleukin (IL)-1β and p-P38/p-NFκB/Cox2/prostaglandin E2 (PGE2) signaling were significantly increased, which stimulated inflammatory responses, whereas cell apoptosis was inhibited due to increased Bcl-2 levels and reduced Caspase3 levels. After MALAT1 was overexpressed in EOC cells, and the cyclin D1, p-PI3K, and p-Akt expressions increased, suggesting the promotion of tumor cell proliferation, while increased zinc finger E-box-binding homeobox-2 (ZEB2), yes-associated protein (YAP), and vimentin expression with E-cadherin downregulation indicated the enhancement of the epithelial-to-mesenchymal transition (EMT) in terms of metastasis, thereby triggering EOC progression. Together, our findings demonstrate how MALAT1 overexpression facilitates an oncogenic function through inhibiting tumor cell apoptosis, combined with increasing tumor cell inflammation, proliferation, and invasion in the EOC tumor microenvironment. MALAT1 is thus a potential diagnostic marker and therapeutic for this malignancy. ? 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Subjects
Cancer-associated fibroblast (CAF); Chemoresistance; Epithelial ovarian cancer (EOC); Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1); Overexpression; Tumorigenesis
SDGs
Other Subjects
histone acetyltransferase; KAT6B protein, human; long untranslated RNA; MALAT1 long non-coding RNA, human; apoptosis; cell motion; cell proliferation; cell transformation; drug resistance; epithelial mesenchymal transition; female; genetics; human; metabolism; ovary tumor; pathology; signal transduction; tumor cell line; tumor invasion; tumor microenvironment; Apoptosis; Carcinoma, Ovarian Epithelial; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Transformation, Neoplastic; Drug Resistance, Neoplasm; Epithelial-Mesenchymal Transition; Female; Histone Acetyltransferases; Humans; Neoplasm Invasiveness; Ovarian Neoplasms; RNA, Long Noncoding; Signal Transduction; Tumor Microenvironment
Publisher
MDPI
Type
journal article