Abstract
IGF2BP1 overexpression promotes hepatocellular carcinoma (HCC) progression. Long non-coding RNA LIN28B-AS1 directly binds to IGF2BP1. In the present study, LIN28B-AS1 and IGF2BP1 expression and their potential functions in HCC cells were tested. Genetic strategies were applied to interfere their expression, and cell survival, proliferation and apoptosis were analyzed. We show that LIN28B-AS1 is expressed in established/primary human HCC cells and HCC tissues. RNA-immunoprecipitation (RIP) and RNA pull-down results confirmed that LIN28B-AS1 directly associated with IGF2BP1 protein in HCC cells. LIN28B-AS1 silencing (by targeted siRNAs) or knockout (KO, by CRISPR-Cas9 method) depleted IGF2BP1-dependent mRNAs (IGF2, Gli1, and Myc), inhibiting HCC cell growth, proliferation, migration, and invasion. Conversely, ectopic overexpression of LIN28B-AS1 upregulated IGF2BP1-dependent mRNAs and promoted HCC cell progression in vitro. Importantly, ectopic IGF2BP1 overexpression failed to rescue LIN28B-AS1-KO HepG2 cells. LIN28B-AS1 siRNA and overexpression were ineffective in IGF2BP1-KO HepG2 cells. In vivo, LIN28B-AS1 KO-HepG2 xenograft tumors grew significantly slower than the control tumors in the nude mice. Taken together, we conclude that LIN28B-AS1 associates with IGF2BP1 to promote human HCC cell progression in vitro and in vivo.
Highlights
Hepatocellular carcinoma (HCC) is a primary cause of cancer-associated human mortalities
LIN28B-AS1 is expressed in human HCC cells and tissues First, we tested expression of LIN28B-AS1 in human
By employing qPCR, we show that LIN28BAS1 is expressed in established (HepG2 cell line) and primary human HCC cells (“HCC1/2”) (Fig. 1a)
Summary
Hepatocellular carcinoma (HCC) is a primary cause of cancer-associated human mortalities. The overall 5-year survival of HCC is far from satisfactory[1,2,3]. Due to the lack of effective treatments, patients with advanced, recurrent and/or metastatic HCCs often have extremely poor prognosis[1,2,3]. HCC incidence has been rising in recent years[1,2,3]. Novel and more efficient anti-HCC strategies are needed[1,2,3]. Insulin-like growth factor 2 (IGF2) mRNA-binding protein 1 (IGF2BP1) is a primary member of the conserved IGF2BP RNA-binding family proteins[4].
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