Long noncoding RNA FAM66C promotes tumor progression and glycolysis in intrahepatic cholangiocarcinoma by regulating hsa‐miR‐23b‐3p/KCND2 axis

Long noncoding RNAs (lncRNAs) are known to be the important regulators in cancer progression. However, the role of lncRNA FAM66C (FAM66C) is yet to be investigated in intrahepatic cholangiocarcinoma (ICC). This study aimed to investigate the effects and related mechanisms of FAM66C in ICC. Human ICC...

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Bibliographic Details
Published in:Environmental toxicology 2021-11, Vol.36 (11), p.2322-2332
Main Authors: Lei, Guang‐Lin, Li, Zhi, Li, Yuan‐Yuan, Hong, Zhi‐Xian, Wang, Sen, Bai, Zhi‐Fang, Sun, Fang, Yan, Jin, Yu, Ling‐Xiang, Yang, Peng‐Hui, Yang, Zhan‐Yu
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Assaying
ATP
Bile Duct Neoplasms - genetics
Bile Ducts, Intrahepatic - metabolism
Cell Line, Tumor
Cell migration
Cell Movement
Cell Proliferation
Cell viability
Cells
Cholangiocarcinoma
Cholangiocarcinoma - genetics
Cholecystokinin
Gene Expression Regulation, Neoplastic
Glycolysis
Glycolysis - genetics
hsa‐miR‐23b‐3p
Humans
Intrahepatic cholangiocarcinoma
KCND2
Lactate
Lactic acid
lncRNA FAM66C
Mice
MicroRNAs - genetics
MicroRNAs - metabolism
Neoplasms
Ribonucleic acid
RNA
RNA, Long Noncoding - genetics
RNA, Long Noncoding - metabolism
Shal Potassium Channels
Tissue
Transfection
Tumors
Xenografts
Xenotransplantation
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Summary:Long noncoding RNAs (lncRNAs) are known to be the important regulators in cancer progression. However, the role of lncRNA FAM66C (FAM66C) is yet to be investigated in intrahepatic cholangiocarcinoma (ICC). This study aimed to investigate the effects and related mechanisms of FAM66C in ICC. Human ICC tissues and cell lines were collected. The expression levels of FAM66C, hsa‐miR‐23b‐3p (miR‐23b‐3p), and KCND2 were detected by qRT‐RCR. The transfection experiments were employed to measure the effect of FAM66C on cell viabilities, migration, and invasion in ICC cells by CCK‐8, transwell assays. Glycolysis was investigated by glucose consumption, lactate production and ATP levels. The dual‐luciferase reporter and RNA pull down assays were conducted as a means of confirming the interactions between FAM66C, miR‐23b‐3p, and KCND2. Furthermore, the levels of the EMT‐associated proteins (KCND2, GLUT1, PKM2, and LDHA) in ICC cells were detected by western blot. FAM66C was increased in ICC tissues and cells, increased cell viability, glycolysis, migration and invasion, and decreased apoptosis were shown in FAM66C overexpressing cells. Mechanistic analyses revealed that FAM66C regulated the downstream target gene KCND2 by sponging miR‐23b‐3p. FAM66C effect on ICC was further validated in murine xenograft assays. FAM66C knockdown cells gave rise to tumors that were smaller in size, consistent with the role of FAM66C as a promoter of in vivo tumor growth. These data revealed that FAM66C was able to drive ICC tumor progression and glycolytic activity via the miR‐23b‐3p/KCND2 axis, indicating FAM66C may be a viable target for treating ICC.
ISSN:1520-4081
1522-7278
DOI:10.1002/tox.23346