Hepatocellular Carcinoma

LINC01013[LncRNA]

miR-6795-5p[miRNA]

FMNL3[mRNA]

hepatocellular carcinoma stem cell

Homo sapiens (human)

Acta Biochim Biophys Sin (Shanghai). 2021 May 21;53(6):652-662. doi: 10.1093/abbs/gmab040.

Novel role of LINC01013/miR-6795-5p/FMNL3 axis in the regulation of hepatocellular carcinoma stem cell features.

Western blot;

Cancer stem cells (CSCs) are major contributors to tumor initiation, recurrence, and metastasis of hepatocellular carcinoma (HCC). Some long non-coding RNAs have been reported as modulators of stem-like properties in cancer cells. However, the role of LINC01013 in liver CSCs has not yet been clarified. In this study, we aimed to elucidate the expression pattern and functions of LINC01013 in HCC. HCC tissues and normal controls were collected, and the expression pattern of LINC01013 and miR-6795-5p was identified by quick real-time polymerase chain reaction. Cell counting kit-8 assay, colony formation, and spheroid formation were performed to measure cell viability, proliferation, and self-renewal of HCC cell lines. The expression of stem markers was detected by western blot analysis. The effect of LINC01013 on viability, proliferation, and stem-like properties was detected through gain-of-function and loss-of-function experiments. The direct interaction among LINC01013, miR-6795-5p, and FMNL3 was testified by dual-luciferase reporter gene assay. Tumor-bearing mice were constructed to ascertain the functions of LINC01013 in vivo. HCC tissues showed increased LINC01013 and FMNL3 expression, while it showed a decreased miR-6795-5p expression as compared to the relative controls. Moreover, the high level of LINC01013 was closely related to the poor prognosis of HCC patients. LINC01013 directly binds to miR-6795-5p and subsequently relieves FMNL3. Silencing LINC01013, FMNL3, or overexpression of miR-6795-5p could suppress spheroid and colony formation, proliferation, as well as expression of stemness markers in HepG2 and SNU-182 cells. LINC01013 knockdown suppressed growth and stem-like traits of HCC cells in vivo by reducing FMNL3 expression. LINC01013/miR-6795-5p/FMNL3 axis may be a novel therapeutic target for HCC.