MicroRNA-33a downregulation is associated with tumorigenesis and poor prognosis in patients with hepatocellular carcinoma

Abstract

Abstract. In order to examine the prognostic significance of miR-33a in patients with hepatocellular carcinoma (HCC), total RNA was extracted from 149 HCC biopsies, 36 of which were paired with para-carcinoma tissues, and miR-33a expression was measured by reverse transcription-quantitative polymerase chain reaction. The results demonstrated that miR-33a expression was decreased in HCC biopsies compared with normal liver tissue samples. It was also demonstrated that miR-33a expression was significantly associated with tumor foci number. Furthermore, overall and progression-free survival time was decreased in patients expressing low miR-33a with multiple tumor foci. Taken together, the low expression of miR-33a may be a potential risk factor for HCC. IntroductionHepatocellular carcinoma (HCC) is the sixth most prevalent cancer worldwide, and is associated with an extremely poor prognosis (1-3). A principal reason for the high mortality of this disease is the failure of early diagnosis for patients with HCC and the lack of effective therapies for patients with HCC in advanced stages. Despite a number of advances made in therapeutic strategies and surgery, the overall prognosis for patients with HCC remains poor due to the high rate of metastasis and recurrence (4-6). Hence, the characterization of the molecular mechanisms in HCC is urgently required to allow the development of novel treatment methods for patients with HCC.MicroRNAs (miRNAs/miRs) are small non-coding RNAs (21-23 nucleotides) that are transcribed as precursors in the nucleus and are subsequently processed into mature miRNAs in the cytoplasm. Mature miRNAs primarily function by sequence specific interactions with the 3'-untranslated regions of mRNAs, leading to the translational suppression or degradation of the mRNAs (7). An increasing number of studies have suggested that miRNAs serve an essential role as prognostic and predictive biomarkers in various types of cancer. For example, miR-1290 and miR-196b have been demonstrated to predict the chemotherapeutic response of patients with lung adenocarcinoma (8). miR-149, an anti-tumor miRNA, has been identified as dysregulated in a variety of types of cancer, including gastric (9), breast (10) and colorectal cancer (11,12).It is also reported that a number of are associated with HCC carcinogenesis, progression and metastasis, including miR-15b (13), miR-122 (14) and miR-29 (15). Furthermore, the low expression of miR-124 is significantly associated with a more aggressive phenotype and a poorer prognosis (16), whereas a high expression of miR-182 has been associated with intrahepatic metastasis and poor prognosis in HCC (17). However, the mechanism of these miRNAs and their regulatory networks in HCC remain elusive, and a number of miRNAs that are associated with HCC have yet to be considered.miR-33a was originally demonstrated to regulate lipid and cholesterol metabolism (18), and is an intronic miRNA located within the sequence of the sterol regulatory element binding protein 2 (SREBP-2) gene. miR-33a ...

Distinctive pattern of AHNAK methylation level in peripheral blood mononuclear cells and the association with HBV‐related liver diseases

“…4,31 On cellular molecular level, both downregulated expression of mir-33a and up-regulated expression of TRIM14 suggest poor prognosis in patients with liver cancer. 37,38 In the current study, significantly decreased promoter methylation level and increased mRNA expression of AHNAK were shown in liver cancer tissues (all P < 0.05), indicating that AHNAK methylation level can be served as a marker for the diagnosis of liver cancer. Collectively, highly expression of AHNAK is associated with the occurrence of liver cancer, which is helpful to the early detection and diagnosis.…”

“…Although the diagnosis and treatment of liver cancer has been better developed, such as surgical resection and liver transplantation, the survival rate is still disappointing . On cellular molecular level, both down‐regulated expression of mir‐33a and up‐regulated expression of TRIM14 suggest poor prognosis in patients with liver cancer . In the current study, significantly decreased promoter methylation level and increased mRNA expression of AHNAK were shown in liver cancer tissues (all P < 0.05), indicating that AHNAK methylation level can be served as a marker for the diagnosis of liver cancer.…”

miR-142-3p as a novel biomarker for predicting poor prognosis in renal cell carcinoma patients after surgery

“…Some of them had already been confirmed to be potential prognostic biomarkers in tumors. 11,[23][24][25] In the present study, we concentrated on miR-142-3p, which had already been proved to be involved in several malignancies. Previous studies have shown miR-142-3p was downregulated in various cancers, such as gastric cancer, cervical cancer, colorectal carcinoma, hepatocellular carcinoma, leukemia, acting as a tumor suppressor.…”

The Role of MicroRNAs in Hepatocellular Carcinoma

“…High expression of miR-92a 25 , miR-221 40 , miR-487a 45 and miR-1468 51 might indicate poor prognosis in HCC. Low expression of miR-33a 63 , miR-122 72 , miR-137 76 , miR-194 90 and miR-940 142 in HCC patients were observed to have unfavorable prognosis. High levels of miR-7/21/107 and low expression of maspin implied poor survival of HBV-related HCC 56 .…”