Role of LncRNA H19 in The Regulation of IGF-1R Expression

Completed

• Conditions: Type 2 Diabetes; Hepatocellular Carcinoma; Cancer
• Interventions: Other: Blood sample collection

• Registration Number: NCT04767750
• Lead Sponsor: Mansoura University

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.

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

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2020-01-01
• Study First Submitted: 2020-12-21
• Status Verified: 2021-02
• Study First Submitted QC: 2021-02-22
• Study First Posted: 2021-02-23
• Primary Completion: 2022-01-30
• Study Completion: 2022-04-04
• Last Update Submitted: 2022-04-05
• Last Update Posted: 2022-04-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 101

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
HCC & T2DM patients	Blood sample collection	Measure lncRNA H19 and IGF-1R mRNA gene expression levels in the collected blood samples.
HCC patients	Blood sample collection	Measure lncRNA H19 and IGF-1R mRNA gene expression levels in the collected blood samples.
Controls	Blood sample collection	Measure lncRNA H19 and IGF-1R mRNA gene expression levels in the collected blood samples.
T2DM patients	Blood sample collection	Measure lncRNA H19 and IGF-1R mRNA gene expression levels in the collected blood samples.

Primary Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (2)

Specialized Medical Hospital, Mansoura University; 🇪🇬 Mansoura, Dakahliya, Egypt

Gastroenterology Center, Mansoura University; 🇪🇬 Mansoura, Dakahliya, Egypt