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

Abstract

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.

A Whole Exon Screening-Based Score Model Predicts Prognosis and Immune Checkpoint Inhibitor Therapy Effects in Low-Grade Glioma

“…Among these risk genes, the specific biological functions of SEL1L3 and CTC548K16.2 are rarely reported. FAM66C is a long noncoding RNA that has been found to regulate glycolysis and inhibit the proliferation and migration of tumor cells ( 45 , 46 ). Consistent with these conclusions, we found that the expression of FAM66C in high-risk patients was significantly lower than that in low-risk patients, suggesting that FAM66C is more likely to play the role of a tumor suppressor gene in tumor cells and prevent tumor progression.…”

ncRNAs-mediated upregulation of GTSE1 is involved in the poor prognosis and tumor immune infiltration of Clear Cell Renal Cell Carcinoma

“…According to this concept, we used the StarBase online tool to forecast 14 miRNAs and then screened two miRNAs, hsa-miR-23b-3p and hsa-miR-532-3p, that were negatively linked with both mRNA and highly expressed in renal paraneoplastic tissues. Although there have been few studies on the role of hsa-mir-23b-3p and hsa-mir-532-3p in renal tumors, it has been reported that hsa-mir-23b-3p is important in cervical cancer and intrahepatic cholangiocarcinoma [33,34] ; Hsa-mir-532-3p can also be used as a biological marker for lung adenocarcinoma prognosis [35] . Further survival analysis indicates that hsa-mir-23b-3p is very important in predicting the prognosis of ccRCC, although hsa-mir-532-3p is not.…”

Lnc-PKD2-2-3/miR-328/GPAM ceRNA Network Induces Cholangiocarcinoma Proliferation, Invasion and 5-FU Chemoresistance

“…Long non-coding RNA (lncRNA), as a newly discovered type of RNA in the current century with a length of more than 200 bp but less protein-coding ability, has been discovered to be closely involved in the pathogenesis of various cancers (11)(12)(13)(14). In the aspect of CCA, several specific lncRNAs have been discovered to participate in CCA initiation or progression (15)(16)(17)(18). For instance, lncRNA SNHG3 promotes CCA cell proliferation and migration via mediating the miR-3173-5p/ERG axis (15); lncRNA FAM66C induces CCA growth, mobility, and glycolysis by modifying miR-23b-3p/KCND2 in vitro and in vivo (16); and lncRNA HOTTIP elevates drug resistance of gemcitabine and cisplatin via sponging miR-637 in CCA (18).…”

“…In the aspect of CCA, several specific lncRNAs have been discovered to participate in CCA initiation or progression (15)(16)(17)(18). For instance, lncRNA SNHG3 promotes CCA cell proliferation and migration via mediating the miR-3173-5p/ERG axis (15); lncRNA FAM66C induces CCA growth, mobility, and glycolysis by modifying miR-23b-3p/KCND2 in vitro and in vivo (16); and lncRNA HOTTIP elevates drug resistance of gemcitabine and cisplatin via sponging miR-637 in CCA (18). However, the engagement of a great number of lncRNAs in CCA is not dragged out, and comprehensive exploration is lacking.…”