MicroRNAs Related to TACE Treatment Response: A Review of the Literature from a Radiological Point of View

Bozzato, Alessandro Marco; Martingano, Paola; Mucelli, R Pozzi; Cavallaro, Marco; Cesarotto, Matteo; Marcello, Cristina; Tiribelli, Claudio; Pascut, Devis; Pizzolato, Riccardo; Mucelli, F. Pozzi; Giuffrè, Mauro; Crocè, Lory Saveria; Cova, Maria Assunta

doi:10.3390/diagnostics12020374

Cited by 11 publications

(9 citation statements)

References 48 publications

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“…Early recurrence mainly results from undetected micrometastases rather than de novo tumors arising in a microenvironment predisposed to carcinogenesis [ 16 ]. Many studies focus on novel biomarkers or other histological characteristics which can predict the early recurrence of HCC [ 23 , 24 , 25 , 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

Predictors of Hepatocellular Carcinoma Early Recurrence in Patients Treated with Surgical Resection or Ablation Treatment: A Single-Center Experience

et al. 2022

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Introduction: Hepatocellular carcinoma (HCC) is the sixth most diagnosed malignancy and the fourth leading cause of cancer-related death worldwide, with poor overall survival despite available curative treatments. One of the most crucial factors influencing survival in HCC is recurrence. The current study aims to determine factors associated with early recurrence of HCC in patients with BCLC Stage 0 or Stage A treated with surgical resection or local ablation. Materials and Methods: We retrospectively enrolled 58 consecutive patients diagnosed with HCC within BCLC Stage 0 or Stage A and treated either by surgical resection or local ablation with maximum nodule diameter < 50 mm. In the first year of follow-up after treatment, imaging was performed regularly one month after treatment and then every three months. Each case was discussed collectively by the Liver Multidisciplinary Group to decide diagnosis, treatment, follow-up, and disease recurrence. Variables resulting in statistically significant difference were then studied by Cox regression analysis; univariately and then multivariately based on forward stepwise Cox regression. Results are represented in hazard ratio (H.R.) with 95% confidence interval (C.I.). Results: There was no statistically significant difference in recurrence rates (34.8 vs. 45.7%, log-rank test, p = 0.274) between patients undergoing surgical resection and local ablation, respectively. Early recurrence was associated with male gender (HR 2.5, 95% C.I. 1.9–3.1), nodule diameter > 20 mm (HR 4.5, 95% C.I. 3.9–5.1), platelet count < 125 × 103 cell/mm3 (HR 1.6, 95% C.I. 1.2–1.9), platelet-lymphocyte ratio < 95 (HR 2.1, 95% C.I. 1.7–2.6), lymphocyte-monocyte ratio < 2.5 (HR 1.9, 95% C.I. 1.4–2.5), and neutrophil-lymphocyte ratio > 2 (HR 2.7, 95% C.I. 2.2–3.3). Discussion and Conclusions: Our results are in line with the current literature. Male gender and tumor nodule dimension are the main risk factors associated with early HCC recurrence. Platelet count and other combined scores can be used as predictive tools for early HCC recurrence, although more studies are needed to define cut-offs.

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Section: Introductionmentioning

confidence: 99%

Predictors of Hepatocellular Carcinoma Early Recurrence in Patients Treated with Surgical Resection or Ablation Treatment: A Single-Center Experience

et al. 2022

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“…In Yang et al, (2013) study, the group compared how the levels of P-glycoprotein in different cell lines affected response to Doxorubicin. In addition, some studies have demonstrated that several miRNAs (miR-1271, miR-4492, miR-214, miR-125b, miR-26a, miR-106b, miR-107, miR-133b, miR-590-5p, miR-21, miR-29a-3p, miR-122, miR-1268a, miR-199a/b-3p, miR-196a2 rs11614913, miR-499a rs3746444, miR-335, miR-10a, miR-23a, miR-24, miR-27a, miR-30c, miR-30e, miR-31, miR-200 a/b, miR-1285-3p, miR-4741, and miR-210) were associated with TACE treatment response (Bozzato et al, 2022).…”

Section: Discussionmentioning

confidence: 98%

Possible Use of miR-223-3p as a Prognostic Marker in Transarterial Chemoembolization Treatment of Hepatocellular Carcinoma Patients

Abdelaziz

El-Guendy

Radwan

et al. 2022

Asian Pac J Cancer Prev

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Introduction and Objectives: Transcatheter chemoembolization (TACE) is the recommended therapy for intermediate stage hepatocellular carcinoma patients. Unfortunately, one of the main reasons for its failure is the emergence of multidrug resistance (MDR). Therefore, this study explored the possibility of using MDR-related miRNA as a response biomarker in HCC patients treated with doxorubicin drug-eluting bead TACE (DEB-TACE). Patients and Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to evaluate the expression level of 14 MDR-related miRNAs in doxorubicin-resistant HepG2 cells (HepG2/Dox) developed by single-dose of doxorubicin mimicking the situation of liver cells surviving TACE. The sera level of miR-223-3p, which was the most significantly downregulated in the HepG2 cells, was determined in 60 primary HCC patients undergoing TACE. Restoring miR-223-3p in HepG2/Dox cell line was achieved by its mimic transfection. Cell sensitivity was measured by SRB assay. Cell apoptosis and doxorubicin uptake were assessed by flow cytometry. The expression of miR-223-3p target protein, P-glycoprotein, was evaluated using qRT-PCR and western blotting. Results: We detected a significant downregulation of circulating miR-223-3p in patients non-responders to TACE treatment compared with responders. The expression of miR-223-3p was markedly decreased in resistant HepG2/Dox cells compared to the parental control. In addition, the expression of miR-223-3p was found to be inversely correlated with P-glycoprotein expression thus confirming the role of miR-223-3p in MDR. Furthermore, overexpression of miR-223-3p suppressed P-glycoprotein which promoted cellular uptake of doxorubicin and increased apoptosis. Conclusions: Our data suggest a potential role for miR-233-3p as a prognostic as well as a therapeutic target for HCC.

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“…Activation of various oncogenes and concurrent defects in endogenous tumor suppressors and pro-apoptotic genes play pivotal roles in uncontrolled tumor growth and apoptosis resistance [ 8 – 16 , 38 – 43 ]. How to effectively suppress oncogenes and simultaneously activate tumor suppressors and pro-apoptotic genes is a big challenge in cancer research field.…”

Section: Discussionmentioning

confidence: 99%

“…Numerous long non-coding RNAs (lncRNAs) have been shown to be involved in tumorigenesis [ 1 – 3 ] and apoptosis in cancer cells [ 4 – 10 ]. Several important tumor-suppressive and pro-apoptotic genes, such as p53 and PTEN, are mutated and/or downregulated in various types of cancer [ 11 , 12 ]; on the other hand, numerous pro-apoptotic genes are deficient in cancers [ 8 , 9 , 13 – 16 ], resulting apoptosis resistance and uncontrolled tumor growth. It is of great interest to identify new endogenous tumor-suppressive and pro-apoptotic lncRNAs that control tumorigenesis and apoptosis.…”

Section: Introductionmentioning

confidence: 99%

The long non-coding RNA keratin-7 antisense acts as a new tumor suppressor to inhibit tumorigenesis and enhance apoptosis in lung and breast cancers

et al. 2023

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Expression of the long non-coding RNA (lncRNA) keratin-7 antisense (KRT7-AS) is downregulated in various types of cancer; however, the impact of KRT7-AS deficiency on tumorigenesis and apoptosis is enigmatic. We aim to explore the influence of KRT7-AS in carcinogenesis and apoptosis. We found that KRT7-AS was deficient in breast and lung cancers, and low levels of KRT7-AS were a poor prognostic factor in breast cancer. Cellular studies showed that silencing of KRT7-AS in lung cancer cells increased oncogenic Keratin-7 levels and enhanced tumorigenesis, but diminished cancer apoptosis of the cancer cells; by contrast, overexpression of KRT7-AS inhibited lung cancer cell tumorigenesis. Additionally, KRT7-AS sensitized cancer cells to the anti-cancer drug cisplatin, consequently enhancing cancer cell apoptosis. In vivo, KRT7-AS overexpression significantly suppressed tumor growth in xenograft mice, while silencing of KRT7-AS promoted tumor growth. Mechanistically, KRT7-AS reduced the levels of oncogenic Keratin-7 and significantly elevated amounts of the key tumor suppressor PTEN in cancer cells through directly binding to PTEN protein via its core nucleic acid motif GGCAAUGGCGG. This inhibited the ubiquitination-proteasomal degradation of PTEN protein, therefore elevating PTEN levels in cancer cells. We also found that KRT7-AS gene transcription was driven by the transcription factor RXRα; intriguingly, the small molecule berberine enhanced KRT7-AS expression, reduced tumorigenesis, and promoted apoptosis of cancer cells. Collectively, KRT7-AS functions as a new tumor suppressor and an apoptosis enhancer in lung and breast cancers, and we unraveled that the RXRα-KRT7-AS-PTEN signaling axis controls carcinogenesis and apoptosis. Our findings highlight a tumor suppressive role of endogenous KRT7-AS in cancers and an important effect the RXRα-KRT7-AS-PTEN axis on control of cancer cell tumorigenesis and apoptosis, and offer a new platform for developing novel therapeutics against cancers.

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MicroRNAs Related to TACE Treatment Response: A Review of the Literature from a Radiological Point of View

Cited by 11 publications

References 48 publications

Predictors of Hepatocellular Carcinoma Early Recurrence in Patients Treated with Surgical Resection or Ablation Treatment: A Single-Center Experience

Predictors of Hepatocellular Carcinoma Early Recurrence in Patients Treated with Surgical Resection or Ablation Treatment: A Single-Center Experience

Possible Use of miR-223-3p as a Prognostic Marker in Transarterial Chemoembolization Treatment of Hepatocellular Carcinoma Patients

The long non-coding RNA keratin-7 antisense acts as a new tumor suppressor to inhibit tumorigenesis and enhance apoptosis in lung and breast cancers

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