Talks
Presenting Author Academic/Professional Position
Mohammad Shabir Hussain
Academic Level (Author 1)
Post-doc
Discipline/Specialty (Author 1)
Cancer and Immunology
Academic Level (Author 2)
Post-doc
Discipline/Specialty (Author 2)
Cancer and Immunology
Academic Level (Author 3)
Post-doc
Discipline/Specialty (Author 3)
Cancer and Immunology
Academic Level (Author 4)
Post-doc
Discipline/Specialty (Author 4)
Cancer and Immunology
Academic Level (Author 5)
Staff
Discipline/Specialty (Author 5)
Cancer and Immunology
Discipline Track
Biomedical Science
Abstract Type
Research/Clinical
Abstract
Background and Aims: The liver is a vital organ involved in metabolism, and liver cancer represents a significant global health challenge, with an expected annual incidence to surpass one million cases worldwide by 2025. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, making up about 90% of cases, and remains the fourth leading cause of cancer-related deaths worldwide. According to the American Cancer Society’s Cancer Facts & Figures 2025, an estimated 42,240 new cases of liver and intrahepatic bile duct cancer and 30,090 deaths are anticipated in the United States in 2025. In Texas, projections forecast 5,930 new cases and 1,400 deaths, ranking it as the second-highest state for liver cancer mortality. Notably, Hispanic populations bear a disproportionate burden of liver cancer, especially in South Texas’ Rio Grande Valley (RGV), a region that is approximately 90% Latino/Hispanic. This area is recognized as a hotspot for multiple types of cancer, driven by a combination of factors including obesity, diabetes, socioeconomic disparities, chronic stress, alcohol-related and non-alcoholic fatty liver disease (NAFLD), along with hepatitis B and C infections. These overlapping risk factors increase the incidence and mortality rates of cancer among this underserved group. Despite the increasing burden, there is limited data on the molecular interactions between new protein biomarkers and oncogenic long noncoding RNAs such as Metastasis-Associated Lung Adenocarcinoma Transcript 1 (lncRNA MALAT1). This is the first study to reveal a strong association between Heterogeneous Nuclear Ribonucleoprotein K (HNRNPK) and lncRNA MALAT1 in HCC. Our previous research using an acute stress model in HCC cell lines treated with cortisol and leptin showed an elevated MALAT1 gene expression. To expand on these findings, we conducted comprehensive proteomics profiling to identify reliable molecular biomarkers associated with the development of HCC.
Methods: Stable SK-Hep1 cell lines overexpressing lncRNA MALAT1 were created and analyzed using high-throughput liquid chromatography-mass spectrometry (LC-MS, Orbitrap Exploris 240). Proteins were identified, quantified, and characterized with Proteome Discoverer 2.5. Differentially expressed proteins were compared with data from the Human Protein Atlas and The Cancer Genome Atlas (TCGA), followed by pathway enrichment analysis using STRING, GeneMANIA, and UniProt databases to assess their functional relevance and relationship with MALAT1 in HCC. Analyses were performed with three biological replicates each from SK-Hep1_MALAT1 and vector control (SK-Hep1_Vec) cell lines. Selected candidate proteins were validated via RT-PCR, Western blotting, and immunohistochemistry (IHC). Phenotypic tests, including invasion, migration, and proliferation assays, were conducted to further characterize the MALAT1-overexpressing and knockdown cell lines.
Results: We identified over 3,500 protein IDs across the samples, including 495 exclusives to SKhep1-MALAT1, 241 in Control, and 1,636 common proteins. Several novel molecules were identified and validated, including 14-3-3 protein epsilon (YWHAE), Importin-7 (IPO7), heterogeneous nuclear ribonucleoprotein K (HNRNPK), Sec1 family domain-containing protein 1 (SCFD1), TIP41-like protein (TIPRL), Serpin B6 (SERPINB6), and Metallothionein-2 (MT2). Interestingly, HNRNPK was exclusively upregulated in MALAT1-overexpressing cells. After proteomics analysis of stress-treated cell lines and investigations in another cancer cell line, we found HNRNPK was significantly upregulated compared to the control and was directly correlated with MALAT1 expression. TCGA analysis confirmed high expression of both HNRNPK and MALAT1 in HCC tissues compared to normal liver tissues, with increased expression linked to advanced disease stages and lymph node metastasis. We also validated TCGA data using clinical samples of the cDNA array.
Conclusion: HNRNPK has emerged as a strong early biomarker for HCC, showing a significant molecular connection with the long non-coding RNA MALAT1. Both MALAT1 and HNRNPK seem to play essential roles in HCC progression, metastasis, and poor clinical outcomes, indicating their potential as targets for early detection and treatment intervention.
Presentation Type
Talk
Recommended Citation
Hussain, Mohammad Shabir; Shaham, Salique H.; Nagati, Veerababu; Anaya, Yamile A.; Chauhan, Subhash C.; and Tripathi, Manish Kumar, "HNRNPK, a potential patient biomarker correlated with LncRNA MALAT1 in Hepatocellular Carcinom" (2025). Research Colloquium. 10.
https://scholarworks.utrgv.edu/colloquium/2025/talks/10
Included in
HNRNPK, a potential patient biomarker correlated with LncRNA MALAT1 in Hepatocellular Carcinom
Background and Aims: The liver is a vital organ involved in metabolism, and liver cancer represents a significant global health challenge, with an expected annual incidence to surpass one million cases worldwide by 2025. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, making up about 90% of cases, and remains the fourth leading cause of cancer-related deaths worldwide. According to the American Cancer Society’s Cancer Facts & Figures 2025, an estimated 42,240 new cases of liver and intrahepatic bile duct cancer and 30,090 deaths are anticipated in the United States in 2025. In Texas, projections forecast 5,930 new cases and 1,400 deaths, ranking it as the second-highest state for liver cancer mortality. Notably, Hispanic populations bear a disproportionate burden of liver cancer, especially in South Texas’ Rio Grande Valley (RGV), a region that is approximately 90% Latino/Hispanic. This area is recognized as a hotspot for multiple types of cancer, driven by a combination of factors including obesity, diabetes, socioeconomic disparities, chronic stress, alcohol-related and non-alcoholic fatty liver disease (NAFLD), along with hepatitis B and C infections. These overlapping risk factors increase the incidence and mortality rates of cancer among this underserved group. Despite the increasing burden, there is limited data on the molecular interactions between new protein biomarkers and oncogenic long noncoding RNAs such as Metastasis-Associated Lung Adenocarcinoma Transcript 1 (lncRNA MALAT1). This is the first study to reveal a strong association between Heterogeneous Nuclear Ribonucleoprotein K (HNRNPK) and lncRNA MALAT1 in HCC. Our previous research using an acute stress model in HCC cell lines treated with cortisol and leptin showed an elevated MALAT1 gene expression. To expand on these findings, we conducted comprehensive proteomics profiling to identify reliable molecular biomarkers associated with the development of HCC.
Methods: Stable SK-Hep1 cell lines overexpressing lncRNA MALAT1 were created and analyzed using high-throughput liquid chromatography-mass spectrometry (LC-MS, Orbitrap Exploris 240). Proteins were identified, quantified, and characterized with Proteome Discoverer 2.5. Differentially expressed proteins were compared with data from the Human Protein Atlas and The Cancer Genome Atlas (TCGA), followed by pathway enrichment analysis using STRING, GeneMANIA, and UniProt databases to assess their functional relevance and relationship with MALAT1 in HCC. Analyses were performed with three biological replicates each from SK-Hep1_MALAT1 and vector control (SK-Hep1_Vec) cell lines. Selected candidate proteins were validated via RT-PCR, Western blotting, and immunohistochemistry (IHC). Phenotypic tests, including invasion, migration, and proliferation assays, were conducted to further characterize the MALAT1-overexpressing and knockdown cell lines.
Results: We identified over 3,500 protein IDs across the samples, including 495 exclusives to SKhep1-MALAT1, 241 in Control, and 1,636 common proteins. Several novel molecules were identified and validated, including 14-3-3 protein epsilon (YWHAE), Importin-7 (IPO7), heterogeneous nuclear ribonucleoprotein K (HNRNPK), Sec1 family domain-containing protein 1 (SCFD1), TIP41-like protein (TIPRL), Serpin B6 (SERPINB6), and Metallothionein-2 (MT2). Interestingly, HNRNPK was exclusively upregulated in MALAT1-overexpressing cells. After proteomics analysis of stress-treated cell lines and investigations in another cancer cell line, we found HNRNPK was significantly upregulated compared to the control and was directly correlated with MALAT1 expression. TCGA analysis confirmed high expression of both HNRNPK and MALAT1 in HCC tissues compared to normal liver tissues, with increased expression linked to advanced disease stages and lymph node metastasis. We also validated TCGA data using clinical samples of the cDNA array.
Conclusion: HNRNPK has emerged as a strong early biomarker for HCC, showing a significant molecular connection with the long non-coding RNA MALAT1. Both MALAT1 and HNRNPK seem to play essential roles in HCC progression, metastasis, and poor clinical outcomes, indicating their potential as targets for early detection and treatment intervention.
