A novel long noncoding RNA, LOC440173, promotes the progression of esophageal squamous cell carcinoma by modulating the miR‐30d‐5p/HDAC9 axis and the epithelial–mesenchymal transition

Abstract

Countless evidence suggests that long noncoding RNAs (lncRNAs) are involved in human malignant cancers, including esophageal squamous cell carcinoma (ESCC), although their exact function remains unclear. In the present study, we aimed to investigate the roles and molecular mechanisms of the lncRNA LOC440173 in ESCC progression. Microarray analysis and quantitative real-time polymerase chain reaction were conducted to measure the expression levels of LOC440173 and miR-30d-5p. The biological function of this lncRNA was investigated using the 3-(4,5dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, clone formation, and transwell assays, as well as flow cytometry and Western blot analysis. The function of LOC440173 was validated in vivo using tumor xenografts. The regulatory network of LOC440173/miR-30d-5p/HDAC9 was established using bioinformatic analysis and verified with dual-luciferase reporter assays, RNA immunoprecipitation assay, and rescue experiments. The expression level of LOC440173 was significantly increased in ESCC tissues and esophageal carcinoma cells. High LOC440173 expression was correlated with histological grade, tumor invasion depth, lymph node metastasis, and TNM stage. Overexpression of LOC440173 promoted esophageal cancer cell proliferation, migration, and invasion, as well as the epithelial-mesenchymal transition (EMT) process in vitro, and facilitated tumor growth in vivo. MicroRNA-30d-5p (miR-30d-5p) was downregulated in ESCC tissues and acted as a direct binding target of LOC440173 during the regulation of HDAC9 expression in esophageal carcinoma cells. In conclusion, LOC440173 exerts a promotive role in ESCC tumorigenesis by targeting the miR-30d-5p/HDAC9 axis and

Histone deacetylase (HDAC) 9: versatile biological functions and emerging roles in human cancer

“…Several recent studies have found that microRNAs (miRs) are involved in post-transcriptional downregulation of HDAC9. Specifically, HDAC9 has been found to be downregulated by miR-188 in bone marrow stromal cells [27], by miR-361-5p in cells associated with cardiac hypertrophy [28], by miR-936 or miR-101-3p in retinoblastoma cells [29,30], by miR-383-5p in gastric carcinoma cells [31], by miR-211-5p in bladder cancer cells [32], by miR-30d-5p in esophageal squamous cell carcinoma cells [33], by miR-509 3p in nonsmall cell lung cancer cells [34] and by miR-377 in oral squamous cell carcinoma cells [35].…”

“…ESSC ranks among the most common and deadly malignant tumors worldwide. Wang et al [33] evaluated the molecular mechanisms underlying the actions of lncRNA LOC440173 in ESCC using both in vitro and in vivo tumor xenograft approaches. They showed that the LOC440173/miR-30d-5p/ HDAC9 regulatory network promoted ESCC tumorigenesis.…”

LINC00261 Suppresses Cisplatin Resistance of Esophageal Squamous Cell Carcinoma Through miR-545-3p/MT1M Axis

“…In addition, the role of lncRNAs in ESCC has also been extensively reported. For example, lncRNA LOC440173 promotes the progression of ESCC by modulating the miR-30d-5p/HDAC9 axis and the epithelial-mesenchymal transition (EMT) (Wang et al, 2020). In addition, lncRNA FOXD2-AS1 promotes DDP-resistance in ESCC by the miR-195/Akt/mTOR PATH (Liu H. et al, 2020).…”

Seven Autophagy-Related lncRNAs Associated With Clinical Prognosis in Hepatocellular Carcinoma.

“…Some studies have also reported that lncRNAs regulate many aspects of cancer progression and affect different malignant behaviors, such as cancer cell proliferation, apoptosis, and metastasis [21,22]. Remarkably, owing to the complexity and diversity, lncRNA's abnormal expression will promote the occurrence of a variety of tumors, such as cervical carcer [23], esophageal squamous cell carcinoma [24], and lung adenocarcinoma [25]. Autophagy has been considered to play a dual and contradictory role in carcinogenesis.…”