Poster Session A   |   11:45am Expo - Hall A & C   |   Poster ID #125

Aspects of LncRNA Malat1 in hepatocellular carcinoma

Academic Research
Prevention, Early Detection, Implementation, and Dissemination
FDA Status:
Not Applicable
CPRIT Grant:
Cancer Site(s):
Liver, Bile Duct, Gallbladder
Sophia Leslie
The University of Texas Rio Grande Valley
Kyle Doxtater
The University of Texas Rio Grande Valley
Amayrani Sanchez
The University of Texas Rio Grande Valley
Subhash C Chauhan
The University of Texas Rio Grande Valley
Manish K Tripathi
The University of Texas Rio Grande Valley


Due to the fast life pace, stress, and a major dietary shift toward preserved food, hepatocellular carcinoma (HCC) incidence and mortality are on a rising trend, thus posing severe concerns. In fact, in 2021, Texas is expected to have the second-highest number of deaths related to liver cancer, with Hispanics having the highest mortality rate. The Rio Grande Valley (RGV) region, where a predominantly (~90%) Latino/Hispanic population resides, has a ~4-fold higher prevalence of liver cirrhosis and is a major hotspot of HCC in the nation. In addition, it was found to be positively correlated with diabetes and obesity. Thus, the RGV region is severely affected by the disproportionate burden of HCC incidence and mortality. As per recent SEER data, the five-year survival rate for this disease drops from 35% to 2% of patients diagnosed with regional and distant stages. Unfortunately, no adequate and specific molecular markers can detect HCC at the early disease onset.


The expression analysis of lncRNA in tissues is typically performed by Q-PCR, which requires primarily frozen tissues, which neither addresses the issue of tumor heterogeneity nor provides information regarding cellular and subcellular localization. Additionally, it is not highly applicable for clinical settings due to the limitation of this method in formalin-fixed paraffin-embedded (FFPE) tissues, which is the primary resource for tissue collection. We have developed and optimized the Z probe-based RNAScope technology (Z-Probe Technology) to address these issues, using unique probes for MALAT1 lncRNA detection.This technology can detect lncRNA on conventional FFPE tissue sections like IHC. Using this technology, we have efficiently detected lncRNA MALAT1 in FFPE HCC tissues, CRC, breast, and pancreatic tumor tissues.TCGA database of HCC patients was also analyzed using the bioinformatic approach. HCC cell lines were profiled for MALAT1 expression using RT-PCR. Lentiviral constructs were used to generate stable lncRNA MALAT1-expressing cell lines. CRISPR/Cas9 constructs were used to knock down lncRNA MALAT1 and NFATc1. ReCLP (Reversible Cross-Linked Precipitation) and iRAP (in vitro RNA Antisense Proteomics) studies are in progress to identify the associated proteins and complexes.


RNAScope analysis showed MALAT1 to be highly over-expressed in human HCC tissues.  MALAT1 expression increased with stage and metastasis. TCGA database analysis confirmed our findings. Multiple NFATc1 binding sites were identified by the ChIPseq database.Overexpression of transcription factor NFATc1 upregulated lncRNA MALAT1 expression. CRISPR/Cas9-based knockdown of NFATc1 downregulated NFATC1 and lncRNA MALAT1, but vice versa was not true, indicating NFATc1 to be upstream of lncRNA MALAT1. Further studies are in progress for the direct association of NFATc1 on the MALAT1 promoter and the mechanism by which the stress factor regulates lncRNA MALAT1 expression.


This study helps to understand MALAT1 expression in different stages of HCC tissues and the influence of biochemical stress factors on long noncoding RNA MALAT1 and different transcription factors. Early diagnosis of these molecular markers will help design novel preventive/therapeutic strategies to reduce HCC progression, metastasis, and hence mortality.