Knockdown by shRNA identifies SLC44A5 as a potential therapeutic target in hepatocellular carcinoma

Abstract

Abstract. Hepatocellular carcinoma (HCC) has been ranked the second leading cause of cancer-associated mortality in China and the third leading cause of cancer-associated mortality worldwide. A number of previous studies investigating SLC44A5 have revealed important biological insight and disease-specific functions. Therefore, the present study investigated the expression of SLC44A5 in HCC tissues and cell lines, and assessed the effect of SLC44A5 on the viability, cell cycle, apoptosis and invasion of HCC cell lines. The mRNA expression of SLC44A5 in 35 HCC tissues was significantly higher compared with that in 35 normal tissues. The protein expression of SLC44A5 was notably high in MHCC-97H and SMMC-7721 cells compared with that in four other HCC cell lines. Knockdown of SLC44A5 using short hairpin RNA inhibited cell viability and arrested the cells in G1 of the cell cycle by reducing the expression of cell cycle markers, proliferating cell nuclear antigen and cyclin-dependent kinase 2 in MHCC-97H and SMMC-7721 cells. Furthermore, SLC44A5 knockdown cells also exhibited cell apoptosis by reducing the expression levels of apoptosis markers, caspase-3 and caspase-9 in MHCC-97H and SMMC-7721 cells, and suppressed invasion. The present results suggested that SLC44A5 is involved in HCC carcinogenesis and progression in HCC, indicating that SLC44A5 may be a molecular target in cancer therapy.

Comparative RNA-Sequencing Analysis Reveals High Complexity and Heterogeneity of Transcriptomic and Immune Profiles in Hepatocellular Carcinoma Tumors of Viral (HBV, HCV) and Non-Viral Etiology

“…Our results are in accordance with data reported in the literature concerning the upregulation/overexpression of SLC genes in HCC, including SLC44A5 and SLC26A6 [38,40], and the downregulated expression of SLC38A4 and SLC22A1 [41,43]. A recent study evidenced SLC26A6 as a novel oncogene in HCC [147].…”

“…SLC44A5 is an intermediate-affinity choline transporter; high expression of SLC44A5 demonstrates its important role in the development and progression of HCC [38]. • SLC26A6 belongs to an anion transporter family [39].…”

Tea and coffee consumption in relation to DNA methylation in four European cohorts

“…It has previously been shown that tea consumption is associated with a lower risk of developing cancer (19,31). In our regional analysis, five cancer-associated genes were differentially methylated with tea consumption in women: THBS2, which has been shown to function as a potent inhibitor of tumour growth (41) and angiogenesis (42); TSPAN32, which is located within an important tumour suppressor region (43); CTBP1, which is involved in promoting the carcinogenesis of human glioma (44); SLC44A5, a potential therapeutic target in hepatocellular carcinoma (45) and CLIC1 that is known to be overexpressed in malignant tumours (46,47) (Table 3).…”

Genomic and transcriptomic correlates of Richter transformation in chronic lymphocytic leukemia

“…Promoter and enhancer regions of other genes expressed in B-cells and with known immune regulatory function and/or involvement in B-cell malignancies (SLC44A5 62,63 , FCRL3 [64][65][66][67] , SELL, TNIP2 68,69 , TRIM13 70,71,72(p13) ) were also affected by kataegis.…”