LINC01638 lncRNA promotes cancer cell proliferation in hepatocellular carcinoma by increasing cancer cell glucose uptake

Abstract

The aim of the present study was to examine the function of long intergenic non-protein coding RNA 1638 (LINC01638) long non-coding RNA (lncRNA) in hepatocellular carcinoma (HCC). In the present study, gene expression was analyzed using qPCR and western blotting. Glucose uptake was analyzed using a glucose uptake assay and cell proliferation was analyzed using a cell counting kit-8 assay. LINC01638 lncRNA and glucose transporter 1 (GLUT1) were upregulated in tumor tissues compared with adjacent healthy tissues of patients with HCC. Expression levels of LINC01638 lncRNA and GLUT1 were positively correlated only in tumor tissues; however, there was no correlation in adjacent healthy tissues. Overexpression of LINC01638 lncRNA and GLUT1 promoted glucose uptake, while LINC01638 lncRNA and GLUT1-knockdown led to inhibited glucose uptake of cells of HCC cell lines. Overexpression of LINC01638 lncRNA mediated the upregulation of GLUT1 expression and accelerated cell proliferation. GLUT1 overexpression failed to significantly affect LINC01638 lncRNA expression, however also promoted cancer cell proliferation. In addition, GLUT1-knockdown attenuated the effects of LINC01638 overexpression on cancer cell proliferation. Therefore, LINC01638 lncRNA promoted cancer cell proliferation in HCC, potentially by increasing cancer cell glucose uptake.

Keywords: glucose transporter 1; glucose uptake; hepatocellular carcinoma; long intergenic non-protein coding RNA 1638; long non-coding RNA.

Figure 1.

LINC01638 lncRNA and GLUT1 mRNA expression levels are upregulated in tumor tissues compared with adjacent healthy tissues in patients with HCC. Compared with adjacent healthy tissues, expression levels of (A) LINC01638 lncRNA and (B) GLUT1 mRNA were significantly higher in the tumor tissues of the 74 patients with HCC *P<0.05. HCC, hepatocellular carcinoma; LINC01638, long intergenic non-protein coding RNA 1638; lncRNA, long non-coding RNA; GLUT1, glucose transporter 1.

Figure 2.

Expression levels of LINC01638 lncRNA and GLUT1 are positively correlated in tumor tissues, but not in adjacent healthy tissues. Expression levels of LINC01638 lncRNA and GLUT1 were significantly and positively correlated in (A) tumor tissues; (B) however, there was no correlation in adjacent healthy tissues. GLUT1, glucose transporter 1; LINC01638, long intergenic non-protein coding RNA 1638; lncRNA, long non-coding RNA.

Figure 3.

LINC01638 lncRNA and GLUT1 promotes glucose uptake in hepatocellular carcinoma cells. (A) Overexpression of LINC01638 lncRNA and GLUT1 led to significantly promoted glucose uptake, while (B) LINC01638 lncRNA and GLUT1-knockdown led to significantly inhibited glucose uptake in SNU-398 and SNU-182 cells. *P<0.05. lncRNA, long non-coding RNA; DPM, disintegrations per minute; C, control cells; NC, negative control siRNA or empty vector; LINC01638, long intergenic non-protein coding RNA 1638; GLUT1, glucose transporter 1; siRNA, small interfering RNA.

Figure 4.

LINC01638 lncRNA is a potential activator of GLUT1 in hepatocellular carcinoma cells. (A) Overexpression of LINC01638 lncRNA led to significantly upregulated GLUT1 expression in SNU-398 and SNU-182 cells. (B) In contrast, GLUT1 overexpression did not significantly affect LINC01638 lncRNA expression in SNU-398 and SNU-182 cells. *P<0.05. lncRNA, long non-coding RNA; LINC01638, long intergenic non-protein coding RNA 1638; C, control cells; NC, negative control empty vector; GLUT1, glucose transporter 1.

Figure 5.

LINC01638 lncRNA promotes the proliferation of HCC cells through GLUT1. (A) GLUT1 siRNA and LINC01638 siRNA were used to knockdown GLUT1 and LINC01638. (B) Overexpression of LINC01638 lncRNA and GLUT1 led a significant promotion of proliferation, while LINC01638 lncRNA and GLUT1-knockdown led to a significant inhibition of proliferation of HCC cells. In addition, GLUT1 knockdown attenuated the enhancing effects of LINC01638 lncRNA overexpression on cancer cell proliferation. *P<0.05. lncRNA, long non-coding RNA; HCC, hepatocellular carcinoma; GLUT1, glucose transporter 1; C, control cells; NC, negative control siRNA; siRNA, small interfering RNA; LINC01638, long intergenic non-protein coding RNA 1638.