Role of LncRNA H19 in The Regulation of IGF-1R Expression
Study Details
Study Description
Brief Summary
Hepatocellular carcinoma (HCC) is a common cancer that poses a heavy economic burden on the healthcare system. In Egypt, it is the most common cause of mortality and morbidity-related cancer. Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia. Cancer and type II diabetes (T2DM), the world's two most prevalent diseases, share many overlapping risk factors and predisposing pathological conditions. The exact mechanisms linking those two diseases are yet to be fully understood.
In this study, the investigators aim to assess the relationship between Long Non-Coding RNA (lncRNA) H19 and Insulin-Like Growth Factor 1 Receptor (IGF-1R) mRNA gene expressions in the blood samples of HCC & T2DM patients to investigate the probability of the presence of a pathophysiological link between HCC and DM that may become a therapeutic target for both diseases. To the investigator's knowledge, there is currently no human research study investigating both H19 and IGF-1R in both DM and cancer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Detailed Description
Hepatocellular carcinoma (HCC) is a common cancer that poses a heavy economic burden on the healthcare system. It represents the fourth and sixth most common cancer in Egypt and worldwide respectively. Globally, HCC is the fourth most common cause of death from cancer. It was estimated to be responsible for nearly 9.1% of the total deaths in 2012 (746,000 deaths). In Egypt, it is the most common cause of cancer-related mortality, and morbidity (32.35% of the total cancer deaths, mortality data were derived from the World Health Organization (WHO)). The leading risk factor in developing HCC in Egypt is hepatitis C virus (HCV).
Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, which may be caused by insufficient insulin secretion, insulin resistance, or augmented glucagon production. Cancer and type II diabetes (T2DM), The world's two most prevalent diseases, share many overlapping risk factors and predisposing pathological conditions. Although the T2DM-cancer co-existence has been noted for many decades, the exact mechanisms linking these diseases are yet to be fully understood.
Insulin-Like Growth Factor-1 Receptor (IGF-1R) is a member of the insulin and IGF family. It coordinates a complex downstream signaling network through which it plays essential roles in the regulation of cell growth, proliferation, and survival as well as in glucose homeostasis. IGF-1R plays a crucial role in many tumor-related courses, such as tumor growth and metastasis in addition to drug resistance. The IGF-1R dysregulated signaling pathways in cancer and DM have been reported to be controlled at different levels by non-coding RNAs.
Non-coding RNAs (ncRNAs) are a large category of RNAs that usually do not participate in protein encoding but have a wide range of biological functions through regulation of protein expression and functions. The two most researched classes of ncRNAs are microRNAs (miRNAs) and the long non-coding RNAs (lncRNAs). H19 is a lncRNA that is found to be overexpressed in many solid tumors including HCC. The relationship between H19 and IGF-1R expression levels in addition to the dysregulation of H19 in DM are still inconsistent in literature, warranting further investigations. Ghazal et al. noted that H19 levels are directly proportional to IGF-1R expression levels in women with endometriosis (Ghazal et al., 2015). This is conflicting with Farzi-Molan et al. who remarked the reverse relation between IGF-1R & H19 during the differentiation of Bone Marrow Mesenchymal Stem Cells (BMSCs) to neural cells
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| HCC patients Measure lncRNA H19 and IGF-1R mRNA gene expression levels in the collected blood samples. |
Other: Blood sample collection
5ml of peripheral blood samples will be collected into tubes containing EDTA from all subjects and the following procedures will be performed:
Peripheral blood mononuclear cells (PBMCs) will be isolated from blood samples.
Total RNA extraction from PBMCs by Trizol reagent and spin column.
Reverse transcription to cDNA.
The expression levels of lncRNA H19, IGF-1R mRNA and GAPDH gene (control gene) will be determined by Real-Time Quantitative PCR
|
| T2DM patients Measure lncRNA H19 and IGF-1R mRNA gene expression levels in the collected blood samples. |
Other: Blood sample collection
5ml of peripheral blood samples will be collected into tubes containing EDTA from all subjects and the following procedures will be performed:
Peripheral blood mononuclear cells (PBMCs) will be isolated from blood samples.
Total RNA extraction from PBMCs by Trizol reagent and spin column.
Reverse transcription to cDNA.
The expression levels of lncRNA H19, IGF-1R mRNA and GAPDH gene (control gene) will be determined by Real-Time Quantitative PCR
|
| HCC & T2DM patients Measure lncRNA H19 and IGF-1R mRNA gene expression levels in the collected blood samples. |
Other: Blood sample collection
5ml of peripheral blood samples will be collected into tubes containing EDTA from all subjects and the following procedures will be performed:
Peripheral blood mononuclear cells (PBMCs) will be isolated from blood samples.
Total RNA extraction from PBMCs by Trizol reagent and spin column.
Reverse transcription to cDNA.
The expression levels of lncRNA H19, IGF-1R mRNA and GAPDH gene (control gene) will be determined by Real-Time Quantitative PCR
|
| Controls Measure lncRNA H19 and IGF-1R mRNA gene expression levels in the collected blood samples. |
Other: Blood sample collection
5ml of peripheral blood samples will be collected into tubes containing EDTA from all subjects and the following procedures will be performed:
Peripheral blood mononuclear cells (PBMCs) will be isolated from blood samples.
Total RNA extraction from PBMCs by Trizol reagent and spin column.
Reverse transcription to cDNA.
The expression levels of lncRNA H19, IGF-1R mRNA and GAPDH gene (control gene) will be determined by Real-Time Quantitative PCR
|
Outcome Measures
Primary Outcome Measures
- Measurement of the gene expression levels of LncRNA H19 & IGF-1R mRNA, normalized to the housekeeping gene GAPDH expression level, in HCC and T2DM in comparison with healthy controls using Real-Time Quantitative PCR (by the 2^-ΔΔCT method). [baseline]
To assess if there is a correlation between lncRNA H19 and IGF-1R mRNA gene expressions in the blood samples of HCC & T2DM patients to investigate the probability of the presence of a pathophysiological link between HCC and DM: To measure the IGF-1R mRNA and lncRNA H19 expression levels in HCC & T2DM patients in comparison with healthy controls. To investigate whether lncRNA H19 and IGF-1R mRNA expression levels affect one another. To compare IGF-1R and lncRNA H19 expression levels in HCC associated with T2DM patients in contrast with sole affection with HCC or T2DM.
Eligibility Criteria
Criteria
• HCC cases (group I):
Inclusion criteria:
- Patients aged 40 years or older with a confirmed diagnosis of HCC through triphasic CT and/or dynamic MRI (European Association for the Study of the Liver, 2012).
Exclusion criteria:
-
Patients who underwent previous cancer-directed treatment (radiation and/or chemotherapy).
-
Patients with any other systemic disease (Renal disease, other primary tumors).
-
T2DM cases (group II):
Inclusion criteria:
- Clinically diagnosed T2DM patients aged 40 years or older frequenting Mansoura Specialized Medical Hospital.
Exclusion criteria:
-
Patients with previous or current malignancies.
-
Patients with diabetic complications (Diabetic retinopathy, neuropathy, nephropathy).
-
Patients with other systemic diseases.
-
HCC & T2DM cases (group III):
Inclusion criteria:
- Patients aged 40 years or older with a confirmed diagnosis of HCC through triphasic CT and/or dynamic MRI and who are clinically diagnosed to have T2DM.
Exclusion criteria:
-
Patients who underwent previous cancer-directed treatment (radiation and/or chemotherapy).
-
Patients with any other systemic disease.
• Controls (group IV):
-
Apparently healthy, age, and gender-matched subjects.
-
No history of malignant disease, diabetes, or HCV.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Gastroenterology Center, Mansoura University | Mansoura | Dakahliya | Egypt | 35516 |
| 2 | Specialized Medical Hospital, Mansoura University | Mansoura | Dakahliya | Egypt | 35516 |
Sponsors and Collaborators
- Mansoura University
Investigators
- Principal Investigator: Noura MS Shehabeldin, M.B.B.Ch, Faculty of Medicine, Mansoura University.
- Study Director: Mohamed AA Zahran, M.D., Faculty of Medicine, Mansoura University.
- Study Chair: Heba K Mohamed, M.D., Faculty of Medicine, Mansoura University.
- Study Chair: Nora M Hussein, M.D., Faculty of Medicine, Mansoura University.
- Study Chair: Ahmed Shehta, M.D., Gastroenterology Center, Mansoura University
- Study Chair: Helmy Ezzat, M.D., Gastroenterology Center, Mansoura University
Study Documents (Full-Text)
None provided.More Information
Additional Information:
- Abudeif, A. (2019) 'Epidemiology and Risk Factors of Hepatocellular Carcinoma in Egypt', Sohag Medical Journal. Sohag University; Faculty of Medicine, 23(3), pp. 8-12.
- Wang, R., Li, K., Xie, Z., Wang, B., Dai, Y., Chen, J.,Ye, Y. (2020) 'Formononetin Induces Apoptosis of PC-3 Human Prostate Cancer Cells via Regulating Long Noncoding RNA H19 and the Mitochondrial Apoptosis Pathway Ruyue', Pharmacogn. Magazine
Publications
- Chen B, Li J, Chi D, Sahnoune I, Calin S, Girnita L, Calin GA. Non-Coding RNAs in IGF-1R Signaling Regulation: The Underlying Pathophysiological Link between Diabetes and Cancer. Cells. 2019 Dec 14;8(12). pii: E1638. doi: 10.3390/cells8121638. Review.
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- Ding J, Li C, Tang J, Yi C, Liu JY, Qiu M. Higher Expression of Proteins in IGF/IR Axes in Colorectal Cancer is Associated with Type 2 Diabetes Mellitus. Pathol Oncol Res. 2016 Oct;22(4):773-9. doi: 10.1007/s12253-016-0065-6. Epub 2016 May 2.
- European Association For The Study Of The Liver; European Organisation For Research And Treatment Of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012 Apr;56(4):908-43. doi: 10.1016/j.jhep.2011.12.001. Erratum in: J Hepatol. 2012 Jun;56(6):1430.
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