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1
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Fagoonee S, Weiskirchen R. MicroRNAs and RNA-Binding Protein-Based Regulation of Bone Metastasis from Hepatobiliary Cancers and Potential Therapeutic Strategies. Cells 2024; 13:1935. [PMID: 39682684 PMCID: PMC11640337 DOI: 10.3390/cells13231935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 11/15/2024] [Accepted: 11/20/2024] [Indexed: 12/18/2024] Open
Abstract
Hepatobiliary cancers, such as hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), are among the deadliest malignancies worldwide, leading to a significant number of cancer-related deaths. While bone metastases from these cancers are rare, they are highly aggressive and linked to poor prognosis. This review focuses on RNA-based molecular mechanisms that contribute to bone metastasis from hepatobiliary cancers. Specifically, the role of two key factors, microRNAs (miRNAs) and RNA-binding proteins (RBPs), which have not been extensively studied in the context of HCC and CCA, is discussed. These molecules often exhibit abnormal expression in hepatobiliary tumors, influencing cancer cell spread and metastasis by disrupting bone homeostasis, thereby aiding tumor cell migration and survival in the bone microenvironment. This review also discusses potential therapeutic strategies targeting these RNA-based pathways to reduce bone metastasis and improve patient outcomes. Further research is crucial for developing effective miRNA- and RBP-based diagnostic and prognostic biomarkers and treatments to prevent bone metastases in hepatobiliary cancers.
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Affiliation(s)
- Sharmila Fagoonee
- Institute of Biostructure and Bioimaging (CNR), Molecular Biotechnology Center “Guido Tarone”, 10126 Turin, Italy
| | - Ralf Weiskirchen
- Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen, D-52074 Aachen, Germany
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2
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Kan LLY, Chan BCL, Yue GGL, Li P, Hon SSM, Huang D, Tsang MSM, Lau CBS, Leung PC, Wong CK. Immunoregulatory and Anti-cancer Activities of Combination Treatment of Novel Four-Herb Formula and Doxorubicin in 4T1-Breast Cancer Bearing Mice. Chin J Integr Med 2024; 30:311-321. [PMID: 37594703 DOI: 10.1007/s11655-023-3745-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/28/2023] [Indexed: 08/19/2023]
Abstract
OBJECTIVE To investigate the in vivo immunomodulatory and anti-tumor mechanisms of the combined treatment of novel Four-Herb formula (4HF) and doxorubicin in triple-negative breast cancer (TNBC). METHODS Murine-derived triple-negative mammary carcinoma cell line, 4T1 cells, was cultured and inoculated into mouse mammary glands. Sixty-six mice were randomly assigned into 6 groups (n=11 in ench): naïve, control, LD 4HF (low dose 4HF), HD 4HF (high dose 4HF), LD 4HF + D (low dose and doxorubicin), and D (doxorubicin). Apart from the naïve group, each mouse received subcutaneous inoculation with 5 × 105 4T1 cells resuspended in 100 µL of normal saline in the mammary fat pads. Starting from the day of tumor cell inoculation, tumors were grown for 6 days. The LD and HD groups received daily oral gavage of 658 and 2,630 mg/kg 4HF, respectively. The LD 4HF+D group received daily oral gavage of 658 mg/kg 4HF and weekly intraperitoneal injection of doxorubicin (5 mg/kg). The D group received weekly intraperitoneal injections of doxorubicin (5 mg/kg). The treatment naïve mice received daily oral gavage of 0.2 mL double distilled water and 0.1 mL normal saline via intraperitoneal injection once a week. The control group received daily oral gavage of 0.2 mL double-distilled water. The treatment period was 30 days. At the end of treatment, mice organs were harvested to analyze immunological activities via immunophenotyping, gene and multiplex analysis, histological staining, and gut microbiota analysis. RESULTS Mice treated with the combination of 4HF and doxorubicin resulted in significantly reduced tumor and spleen burdens (P<0.05), altered the hypoxia and overall immune lymphocyte landscape, and manipulated gut microbiota to favor the anti-tumor immunological activities. Moreover, immunosuppressive genes, cytokines, and chemokines such as C-C motif chemokine 2 and interleukin-10 of tumors were significantly downregulated (P<0.05). 4HF-doxorubicin combination treatment demonstrated synergetic activities and was most effective in activating the anti-tumor immune response (P<0.05). CONCLUSION The above results provide evidence for evaluating the immune regulating mechanisms of 4HF in breast cancer and support its clinical significance in its potential as an adjunctive therapeutic agent or immune supplement.
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Affiliation(s)
- Lea Ling-Yu Kan
- Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
- State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Hong Kong, China
| | - Ben Chung-Lap Chan
- Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
- State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Hong Kong, China
| | - Grace Gar-Lee Yue
- Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
- State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Hong Kong, China
| | - Peiting Li
- Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
- State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Hong Kong, China
| | - Sharon Sze-Man Hon
- Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Danqi Huang
- Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Miranda Sin-Man Tsang
- Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
- State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Hong Kong, China
- China-Australia International Research Centre for Chinese Medicine, School of Health and Biomedical Sciences, STEM College, RMIT University, Bundoora, Victoria, Australia
| | - Clara Bik-San Lau
- Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
- State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Hong Kong, China
| | - Ping-Chung Leung
- Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
- State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Hong Kong, China
| | - Chun-Kwok Wong
- Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
- State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Hong Kong, China.
- Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong SAR, China.
- Li Dak Sum Yip Yio Chin R & D Centre for Chinese Medicine, The Chinese University of Hong Kong SAR, Hong Kong, China.
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He X, Fu J, Lyu W, Huang M, Mo J, Cheng Y, Xu Y, Zheng L, Zhang X, Qi L, Zhang L, Zheng Y, Huang M, Ni L, Lu J. Identification of Bulbocodin D and C as novel STAT3 inhibitors and their anticancer activities in lung cancer cells. Chin J Nat Med 2023; 21:842-851. [PMID: 38035939 DOI: 10.1016/s1875-5364(23)60521-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Indexed: 12/02/2023]
Abstract
Cancer stands as one of the predominant causes of mortality globally, necessitating ongoing efforts to develop innovative therapeutics. Historically, natural products have been foundational in the quest for anticancer agents. Bulbocodin D (BD) and Bulbocodin C (BC), two bibenzyls derived from Pleione bulbocodioides (Franch.) Rolfe, have demonstrated notable in vitro anticancer activity. In human lung cancer A549 cells, the IC50s for BD and BC were 11.63 and 11.71 μmol·L-1, respectively. BD triggered apoptosis, as evidenced by an upsurge in Annexin V-positive cells and elevated protein expression of cleaved-PARP in cancer cells. Furthermore, BD and BC markedly inhibited the migratory and invasive potentials of A549 cells. The altered genes identified through RNA-sequencing analysis were integrated into the CMap dataset, suggesting BD's role as a potential signal transducer and activator of transcription 3 (STAT3) inhibitor. SwissDock and MOE analyses further revealed that both BD and BC exhibited a commendable binding affinity with STAT3. Additionally, a surface plasmon resonance assay confirmed the direct binding affinity between these compounds and STAT3. Notably, treatment with either BD or BC led to a significant reduction in p-STAT3 (Tyr 705) protein levels, regardless of interleukin-6 stimulation in A549 cells. In addition, the extracellular signal-regulated kinase (ERK) was activated after BD or BC treatment. An enhancement in cancer cell mortality was observed upon combined treatment of BD and U0126, the MEK1/2 inhibitor. In conclusion, BD and BC emerge as promising novel STAT3 inhibitors with potential implications in cancer therapy.
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Affiliation(s)
- Xinyu He
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China
| | - Jiarui Fu
- College of Plant Protection, Fujian Agriculture and Forestry University, Fuzhou 350002, China
| | - Wenyu Lyu
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China
| | - Muyang Huang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China
| | - Jianshan Mo
- National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation, Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China
| | - Yaxin Cheng
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China
| | - Yulian Xu
- College of Life Sciences, China Jiliang University, Hangzhou 310018, China
| | - Lijun Zheng
- Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou 350100, China
| | - Xiaolei Zhang
- National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation, Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China
| | - Lu Qi
- Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Lele Zhang
- School of Basic Medical Sciences, Chengdu University, Chengdu 610106, China
| | - Ying Zheng
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China
| | - Mingqing Huang
- College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350003, China.
| | - Lin Ni
- College of Plant Protection, Fujian Agriculture and Forestry University, Fuzhou 350002, China.
| | - Jinjian Lu
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China; Department of Pharmaceutical Sciences, Faculty of Health Sciences, University of Macau, Macao 999078, China; Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, University of Macau, Macao 999078, China.
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Shehab-Eldeen S, Metwaly MF, Saber SM, El-Kousy SM, Badr EAE, Essa A. MicroRNA-29a and MicroRNA-124 as novel biomarkers for hepatocellular carcinoma. Dig Liver Dis 2023; 55:283-290. [PMID: 35525722 DOI: 10.1016/j.dld.2022.04.015] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 04/19/2022] [Accepted: 04/21/2022] [Indexed: 02/01/2023]
Abstract
BACKGROUND Numerous microRNAs (miRNAs) have been observed to be abnormally expressed in cancer. Therefore, miRNA signatures could be potential noninvasive diagnostic and prognostic biomarkers for hepatocellular carcinoma (HCC). AIMS To correlate miRNA-29a and miRNA-124 expression levels with the clinical features and survival rates of HCC patients. METHODS Serum miRNA expression in 150 samples (50 patients with HCC, 50 patients with liver cirrhosis, and 50 healthy controls) were quantified using real-time qRT-PCR. RESULTS The expression levels of serum miRNA-29a were higher and the levels of miRNA-124 were lower in patients with HCC than in patients with liver cirrhosis and controls. ROC curve analysis showed promising accuracy for both miRNAs in distinguishing patients with HCC from those with liver cirrhosis. Levels of miRNA-29a were related to tumor number, size, stage, and outcome, whereas levels of miRNA-124 were related to vascular invasion. The overall survival rate of patients with low miRNA-29a expression was significantly higher than that of patients with high expression. Additionally, the multivariate analysis identified miRNA-29a as an independent prognostic variable. CONCLUSIONS The investigated miRNAs showed acceptable accuracy in the diagnosis of HCC; therefore, both could be utilized as diagnostic biomarkers. Additionally, miRNA-29a could be used as a prognostic biomarker.
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Affiliation(s)
- Somaia Shehab-Eldeen
- Tropical Medicine Department, Faculty of Medicine, Menoufia University, Shebin El-Kom 32511, Egypt; Internal Medicine Department, College of Medicine, King Faisal University, Al-Ahsaa 31982, Saudi Arabia.
| | - Mohamed F Metwaly
- Chemist at Faculty of Science, Menoufia University, Shebin El-Kom 32511, Egypt
| | - Safa M Saber
- Chemist at Clinical Laboratory Department, Student hospital, Menoufia University, Shebin El-Kom 32511, Egypt
| | - Salah M El-Kousy
- Organic Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Kom 32511, Egypt
| | - Eman A E Badr
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Menoufia University, Shebin El-Kom 32511, Egypt
| | - Abdallah Essa
- Tropical Medicine Department, Faculty of Medicine, Menoufia University, Shebin El-Kom 32511, Egypt; Internal Medicine Department, College of Medicine, King Faisal University, Al-Ahsaa 31982, Saudi Arabia
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Lai HC, Lin HJ, Jeng LB, Huang ST. Roles of conventional and complementary therapies in recurrent hepatocellular carcinoma. World J Gastrointest Oncol 2023; 15:19-35. [PMID: 36684056 PMCID: PMC9850766 DOI: 10.4251/wjgo.v15.i1.19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Revised: 11/03/2022] [Accepted: 12/07/2022] [Indexed: 01/10/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common type of cancer and the fourth leading cause of cancer-related deaths in the world. HCC has a reported recurrence rate of 70%-80% after 5 years of follow-up. Controlling tumor recurrence is the most critical factor associated with HCC mortality. Conventional salvage therapies for recurrent HCC include re-hepatectomy or liver transplantation, transcatheter arterial chemoembolization, Y-90, target therapy, and immunotherapy; however, these conventional treatment modalities have yet to achieve consistently favorable outcomes. Meanwhile, previous studies have demonstrated that conventional therapies in combination with traditional Chinese medicine (TCM), acupuncture, moxibustion or dietary supplements could notably benefit patients with HCC recurrence by strengthening and augmenting the overall management strategy. However, systemic reviews related to the interactions between complementary therapies and conventional therapy in recurrent HCC are limited. In this review, we discuss the molecular mechanisms underlying the functions of complementary therapies for recurrent HCC, which include augmenting the local control to improve the congestion status of primary tumors and reducing multicentric tumor occurrence via inducing autophagy, apoptosis or cell cycle arrest. TCM and its derivatives may play important roles in helping to control HCC recurrence by inhibiting epithelial-mesenchymal transition, migration, invasion, and metastasis, inhibiting cancer stem cells, and ameliorating drug resistance.
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Affiliation(s)
- Hsiang-Chun Lai
- Graduate Institute of Chinese Medicine, School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 40447, Taiwan
- Department of Chinese Medicine, China Medical University Hospital, Taichung 40447, Taiwan
| | - Hung-Jen Lin
- Department of Chinese Medicine, China Medical University Hospital, Taichung 40447, Taiwan
| | - Long-Bin Jeng
- Organ Transplantation Center, China Medical University Hospital, Taichung 40447, Taiwan
| | - Sheng-Teng Huang
- Department of Chinese Medicine, China Medical University Hospital, Taichung 40447, Taiwan
- School of Chinese Medicine, China Medical University, Taichung 40447, Taiwan
- Cancer Research Center for Traditional Chinese Medicine, Department of Medical Research, China Medical University Hospital, Taichung 40447, Taiwan
- An-Nan Hospital, China Medical University, Tainan 709204, Taiwan
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Wu W, Lu P, Huang Y, Zhu Z, Li C, Liu Y. Emodin regulates the autophagy via the miR-371a-5p/PTEN axis to inhibit hepatic malignancy. Biochem Biophys Res Commun 2022; 619:1-8. [PMID: 35724456 DOI: 10.1016/j.bbrc.2022.06.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Revised: 05/27/2022] [Accepted: 06/03/2022] [Indexed: 11/28/2022]
Abstract
Emodin has been reported to fulfill an important function in suppressing the vicious outcome of liver cancer. We aimed to elucidate the partial underlying molecular mechanism of emodin in inhibiting liver cancer, and we applied miRNA-sequence analysis and corresponding molecular functional experiments to find that the inhibitory effect of emodin on liver cancer was partly mediated by cellular autophagy through the miR-371a-5p/PTEN axis. The expression level of miR-371a-5p was down-regulated after emodin treatment in liver cancer cell lines (LCCLs). Restoring the expression level of miR-371a-5p attenuated the suppression of emodin on LCCLs. Additionally, we performed the prediction in relevant online databases and found that PTEN might functioned as a downstream target of miR-371a-5p to participate in the regulation on the above process. What's more, the detection of autophagy-related protein markers showed that LC3II was elevated accompanied by the decreased P62. The above results revealed that PTEN functioned as a key target to regulate the autophagy in the process where emodin inhibited the malignant outcome of LCCLs via miR-371a-5p, which further provided a theoretical basis for the application of traditional Chinese medicine (TCM) on clinical tumors.
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Affiliation(s)
- Wu Wu
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Peilin Lu
- Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yujing Huang
- Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zhu Zhu
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Chunming Li
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yiming Liu
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
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Yang YL, Tsai MC, Chang YH, Wang CC, Chu PY, Lin HY, Huang YH. MIR29A Impedes Metastatic Behaviors in Hepatocellular Carcinoma via Targeting LOX, LOXL2, and VEGFA. Int J Mol Sci 2021; 22:ijms22116001. [PMID: 34206143 PMCID: PMC8199573 DOI: 10.3390/ijms22116001] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 05/29/2021] [Accepted: 05/31/2021] [Indexed: 12/16/2022] Open
Abstract
Primary liver cancer accounts for the third most deadly type of malignant tumor globally, and approximately 80% of the cases are hepatocellular carcinoma (HCC), which highly relies on the activity of hypoxia responsive pathways to bolster its metastatic behaviors. MicroRNA-29a (MIR29A) has been shown to exert a hepatoprotective effect on hepatocellular damage and liver fibrosis induced by cholestasis and diet stress, while its clinical and biological role on the activity hypoxia responsive genes including LOX, LOXL2, and VEGFA remains unclear. TCGA datasets were retrieved to confirm the differential expression and prognostic significance of all genes in the HCC and normal tissue. The Gene Expression Omnibus (GEO) dataset was used to corroborate the differential expression and diagnostic value of MIR29A. The bioinformatic identification were conducted to examine the interaction of MIR29A with LOX, LOXL2, and VEGFA. The suppressive activity of MIR29A on LOX, LOXL2, and VEGF was verified by qPCR, immunoblotting, and luciferase. The effect of overexpression of MIR29A-3p mimics in vitro on apoptosis markers (caspase-9, -3, and poly (ADP-ribose) polymerase (PARP)); cell viability and wound healing performance were examined using immunoblot and a WST-1 assay and a wound healing assay, respectively. The HCC tissue presented low expression of MIR29A, yet high expression of LOX, LOXL2, and VEGFA as compared to normal control. Serum MIR29A of HCC patients showed decreased levels as compared to that of normal control, with an area under curve (AUC) of 0.751 of a receiver operating characteristic (ROC) curve. Low expression of MIR29A and high expression of LOX, LOXL2, and VEGFA indicated poor overall survival (OS). MIR29A-3p was shown to target the 3'UTR of LOX, LOXL2, and VEGFA. Overexpression of MIR29A-3p mimic in HepG2 cells led to downregulated gene and protein expression levels of LOX, LOXL2, and VEGFA, wherein luciferase reporter assay confirmed that MIR29A-3p exerts the inhibitory activity via directly binding to the 3'UTR of LOX and VEGFA. Furthermore, overexpression of MIR29A-3p mimic induced the activity of caspase-9 and -3 and PARP, while it inhibited the cell viability and wound healing performance. Collectively, this study provides novel insight into a clinical-applicable panel consisting of MIR29, LOX, LOXL2, and VEGFA and demonstrates an anti-HCC effect of MIR29A via comprehensively suppressing the expression of LOX, LOXL2, and VEGFA, paving the way to a prospective theragnostic approach for HCC.
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Affiliation(s)
- Ya-Ling Yang
- Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan;
| | - Ming-Chao Tsai
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan;
| | - Yen-Hsiang Chang
- Department of Nuclear Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan;
- Center for Mitochondrial Research and Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - Chen-Chen Wang
- Research Assistant Center, Show Chwan Memorial Hospital, Changhua 500, Taiwan;
| | - Pei-Yi Chu
- Department of Pathology, Show Chwan Memorial Hospital, Changhua 500, Taiwan
- School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan
- Department of Health Food, Chung Chou University of Science and Technology, Changhua 510, Taiwan
- National Institute of Cancer Research, National Health Research Institutes, Tainan 704, Taiwan
- Correspondence: (P.-Y.C.); (H.-Y.L.); (Y.-H.H.); Tel.: +886-9-75611505 (H.-Y.L.)
| | - Hung-Yu Lin
- Research Assistant Center, Show Chwan Memorial Hospital, Changhua 500, Taiwan;
- Correspondence: (P.-Y.C.); (H.-Y.L.); (Y.-H.H.); Tel.: +886-9-75611505 (H.-Y.L.)
| | - Ying-Hsien Huang
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
- Correspondence: (P.-Y.C.); (H.-Y.L.); (Y.-H.H.); Tel.: +886-9-75611505 (H.-Y.L.)
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New Insights into the Role of miR-29a in Hepatocellular Carcinoma: Implications in Mechanisms and Theragnostics. J Pers Med 2021; 11:jpm11030219. [PMID: 33803804 PMCID: PMC8003318 DOI: 10.3390/jpm11030219] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 03/11/2021] [Accepted: 03/16/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) remains one of the most lethal human cancer globally. For advanced HCC, curable plan for advanced HCC is yet to be established, and the prognosis remains poor. The detail mechanisms underlying the progression of HCC tumorigenicity and the corruption of tumor microenvironment (TME) is complex and inconclusive. A growing body of studies demonstrate microRNAs (miRs) are important regulators in the tumorigenicity and TME development. Notably, mounting evidences indicate miR-29a play a crucial role in exerting hepatoprotective effect on various types of stress and involved in the progression of HCC, which elucidates their potential theragnostic implications. In this review, we reviewed the advanced insights into the detail mechanisms by which miR-29a dictates carcinogenesis, epigenetic program, and metabolic adaptation, and implicated in the sponging activity of competitive endogenous RNAs (ceRNA) and the TME components in the scenario of HCC. Furthermore, we highlighted its clinical significance in diagnosis and prognosis, as well as the emerging therapeutics centered on the activation of miR-29a.
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