The DIS3L2 Knockout SK-HEP-1 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population generated from the SK-HEP-1 human hepatocellular carcinoma cell line, in which the gene encoding DIS3L2 has been disrupted. This heterogeneous pool of cells harbors diverse loss-of-function mutations at the target locus, enabling robust loss-of-function studies without clonal isolation. The model is designed for investigating the roles of DIS3L2 in RNA metabolism within a liver cancer context.
SK-HEP-1 is a widely used hepatocellular carcinoma cell line originally established from the ascitic fluid of a male patient with liver adenocarcinoma. These cells serve as a standard in vitro system for studying hepatic tumorigenesis, drug responses, and molecular mechanisms underlying liver cancer. Their tumor-derived background provides a pathologically relevant environment for examining the tumor-suppressive functions of RNA surveillance factors.
DIS3L2 encodes a 3′-5′ exoribonuclease that selectively degrades RNAs bearing 3′-terminal oligouridine tails. This activity is directed by ZCCHC6 (TUT7) and ZCCHC11 (TUT4), terminal uridylyl transferases that uridylate pre-let-7 and miR-200 family microRNAs. The LIN28A/LIN28B proteins promote pre-let-7 uridylation, thereby channeling these transcripts toward DIS3L2-mediated decay. Thus, DIS3L2 functions as a key effector in microRNA biogenesis control and broader cytoplasmic RNA surveillance. Its loss leads to accumulation of uridylated RNAs, disrupting gene expression networks relevant to development and cancer.
In hepatocellular carcinoma, DIS3L2 has been implicated as a putative tumor suppressor, and its inactivation may foster oncogenic transformation. The SK-HEP-1 polyclonal knockout model allows dissection of how DIS3L2 loss impacts RNA metabolism and cellular phenotypes in a liver cancer milieu. Researchers can probe the interplay between RNA decay pathways and tumor cell behavior, including proliferation, apoptosis, and metastatic potential, using this disease-relevant platform.
Research applications include RT-qPCR quantification of pre-let-7 and miR-200 family members, RNA sequencing to identify DIS3L2 substrates, and cRT-PCR for uridylation detection. Western blotting validates DIS3L2 knockout, while RNA stability and functional assays probe consequences on proliferation and apoptosis. The polyclonal knockout cells are suited for Perlman syndrome studies, tumor suppression mechanisms, and development of RNA-targeted drugs. For further details or custom inquiries, contact Ascent Research.