Article
Biochemistry & Molecular Biology
Chunfeng Liu, Matjaz Rokavec, Zekai Huang, Heiko Hermeking
Summary: This study reveals that curcumin can activate the KEAP1/NRF2/ARE pathway and induce ROS to upregulate the expression of miR-34 in colorectal cancer cells. Curcumin can also inhibit migration and invasion of cancer cells and promote mesenchymal-epithelial transition by activating this pathway. Therefore, activation of the KEAP1/NRF2/miR-34 axis may contribute to the tumor suppressive effects of curcumin.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Biochemistry & Molecular Biology
Zekai Huang, Markus Kaller, Heiko Hermeking
Summary: miR-34a and miR-34b/c, as direct targets of p53, play a crucial role in the tumor suppressive effects of p53. Inactivating miR-34a and/or miR-34b/c in colorectal cancer cell line HCT116 had significant effects on proliferation, migration, invasion, chemosensitivity, autophagy, and apoptosis. The concomitant deletion of miR-34a and miR-34b/c resulted in EMT signature enrichment, impaired gene repression by the p53-DREAM pathway, and elevated autophagy. A gene signature upregulated in cells with combined inactivation of miR-34a and miR-34b/c was associated with invasive colon cancer subtype CMS4, poor overall survival in CRC patients, and 5-FU resistance in CRC cell lines.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Biochemistry & Molecular Biology
Sophie Mockly, Elisabeth Houbron, Herve Seitz
Summary: miR-34a does not meet the definition of tumor suppressor miRNAs, as it is not down-regulated in primary tumors and does not exhibit anti-tumorigenic activity. Therefore, synthetic administration of miR-34a is not efficient against solid tumors.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Cell Biology
Chunfeng Liu, Matjaz Rokavec, Zekai Huang, Heiko Hermeking
Summary: Aspirin and its active metabolite salicylate have shown potential in preventing and suppressing the progression of colorectal cancer. The study found that salicylate can induce the expression of tumor suppressive microRNAs miR-34a and miR-34b/c in a p53-independent manner, through the activation of AMPK and NRF2 pathways. The activation of these microRNAs by salicylate is important for its inhibitory effects on migration, invasion, and metastasis formation by colorectal cancer cells.
CELL DEATH & DISEASE
(2023)
Article
Cell Biology
Qiumin Xu, Jieying Xu, Yifan Wu
Summary: Acute lung injury (ALI) is associated with severe lung inflammation. GPR43 plays a role in mediating lung injury through the JNK/ELK1 pathway, and targeting GPR43 may have therapeutic potential against ALI.
INFLAMMATION RESEARCH
(2022)
Article
Medicine, Research & Experimental
Nastaran Injinari, Zeinab Amini-Farsani, Mahtab Yadollahi-Farsani, Hossein Teimori
Summary: miR-34a and miR-520h are implicated in the apoptosis pathways, with decreased expression in cancer tissues and VPA inducing apoptosis and affecting their expression. VPA can be a possible option in breast cancer research due to its impact on the regulation of miRNAs and HDAC1.
Article
Multidisciplinary Sciences
Livia Bassani Lins de Miranda, Keli Lima, Juan Luiz Coelho-Silva, Fabiola Traina, Susumu S. Kobayashi, Joao Agostinho Machado-Neto
Summary: The compound NT157 has been found to inhibit the growth and migration of lung cancer cells, induce apoptosis, and suppress signaling pathways. At the molecular level, NT157 reduces the expression of oncogenes and increases the expression of genes related to cellular stress and apoptosis. It was also discovered that JNK plays a key role in NT157-induced phosphorylation of IRS1 and IRS2. Additionally, NT157 has synergistic effects with EGFR inhibitors.
SCIENTIFIC REPORTS
(2022)
Article
Medicine, Research & Experimental
Qiuxia Li, Quanjiang Zhang
Summary: MicroRNAs (miRNAs) are small endogenous RNAs that regulate gene expression by binding to the mRNAs of protein-coding genes. In endothelial cells, miR-34a is an early identified miRNA that plays important roles in regulating endothelial functions, angiogenesis, differentiation, senescence, inflammatory response, responses to shear stress, and mitochondrial function. This review provides an overview of the current understanding of miR-34a in endothelial biology and discusses its potential as a therapeutic target for vascular diseases.
Article
Oncology
Hao-Gang Zhang, Fu-Jing Wang, Yao Wang, Zi-Xing Zhao, Peng-Fei Qiao
Summary: The study reveals that in colorectal cancer (CRC) progression, GAS5 forms a negative feedback loop with miR-34a to regulate macroautophagy in CRC cells suppressed by GAS5, inducing apoptosis through the mTOR/SIRT1 pathway.
Article
Plant Sciences
Yicun Han, Xiuqi Fan, Liyan Fan, Yaosong Wu, Zhexu Zhou, Ge Wang, Lanwei Guo, Wendong Gao, Yulong Chen, Qilong Gao
Summary: This study aims to investigate the mechanism of action of the traditional Chinese medicine, Liujunzi decoction, in the treatment of oesophageal squamous cell carcinoma. The results show that Liujunzi decoction exerts its excellent antitumor effect by interfering with the miR-34a/STAT3/IL-6R feedback loop and augmenting antitumor immune responses. This provides new insights into the mechanisms of Liujunzi decoction and sheds light on the multifaceted role of phytomedicine in cancer.
Article
Environmental Sciences
Rili Hao, Junlin Ge, Xinyu Song, Feng Li, Dongxiao Sun-Waterhouse, Dapeng Li
Summary: This study revealed that cadmium can induce cytotoxicity and neurotoxicity in PC12 cells through both apoptosis and ferroptosis, with involvement of the miR-34a-5p/Sirt1 axis. Knocking out miR-34a-5p alleviated cadmium-induced damage, highlighting the critical role of miRNAs as regulators in cadmium toxicity.
ENVIRONMENTAL TOXICOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ying Xiao, Xiaozhou Li, Shuangfa Qiu, Yongjun Wang, Dongshan Zhang
Summary: This study found that lncRNA122049 can protect renal cells from apoptosis in ischemic kidney injury by regulating the miR-330-5p/ELK1 axis.
Article
Medicine, Research & Experimental
Marianna Abate, Angela Lombardi, Amalia Luce, Manuela Porru, Carlo Leonetti, Marco Bocchetti, Virginia Campani, Giuseppe De Rosa, Sossio Fabio Graziano, Valeria Nele, Francesco Cardile, Federica Zito Marino, Renato Franco, Andrea Ronchi, Marianna Scrima, Rossella Sperlongano, Roberto Alfano, Gabriella Misso, Evzen Amler, Michele Caraglia, Silvia Zappavigna
Summary: This study demonstrates that nanodiamonds can effectively deliver miRNA to inhibit tumor development and progression. The nanodiamonds have excellent biocompatibility, and the miR-34a conjugated with nanodiamonds can effectively inhibit cancer cell proliferation and migration. Furthermore, the miR-34a-conjugated nanodiamonds exhibit remarkable anti-tumor effects in mouse models.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Article
Cell Biology
Yin Zhang, Ye-Ya Tan, Pei-Pei Chen, Hui Xu, Shu-Juan Xie, Shi-Jun Xu, Bin Li, Jun-Hao Li, Shun Liu, Jian-Hua Yang, Hui Zhou, Liang-Hu Qu
Summary: Liver development is a complex process involving the interplay of epigenetic regulators, transcription factors, and miRNAs. This study identified the genome-wide miRNA targetomes during mouse liver development and revealed a novel mechanism of terminal differentiation of hepatocytes regulated by the miR-122/Hippo pathway. The findings provide insights into the function of miR-122 in liver pathology, particularly in processes like inflammation, fibrosis, and hepatocellular carcinoma.
CELL DEATH & DISEASE
(2021)
Article
Cell Biology
David E. Adams, Yuxuan Zhen, Xiaoyang Qi, Wen-Hai Shao
Summary: Axl receptor tyrosine kinase plays a role in inflammatory renal diseases by promoting glomerular proliferation. The expression of Axl in the kidney is regulated by transcription factors and secondary structures. MiRNA-34a negatively regulates Axl expression.
Editorial Material
Gastroenterology & Hepatology
Ann-Lii Cheng
Summary: In 2020, combination treatments have significantly improved the efficacy of systemic therapy for HCC, with different drug combinations showing high therapeutic effects, establishing new standards and directions for future treatment of HCC.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2021)
Article
Oncology
Kuo-Hsing Chen, Liang-In Lin, Chang-Tsu Yuan, Li-Hui Tseng, Yu-Liang Chao, Yi-Hsin Liang, Jin-Tung Liang, Been-Ren Lin, Ann-Lii Cheng, Kun-Huei Yeh
Summary: In Taiwan, distinct clinicopathological features were identified for CIMP-high CRC among different age groups. Our data suggest the association between BMI >= 27.5 kg/m(2) and CIMP-high CRC in patients younger than 50 years.
BRITISH JOURNAL OF CANCER
(2021)
Article
Oncology
Baek-Yeol Ryoo, Ann-Li Cheng, Zhenggang Ren, Tae-You Kim, Hongming Pan, Kun-Ming Rau, Hye Jin Choi, Joong-Won Park, Jee Hyun Kim, Chia Jui Yen, Ho Yeong Lim, Dongli Zhou, Josef Straub, Juergen Scheele, Karin Berghoff, Shukui Qin
Summary: This study evaluated the efficacy of the MET inhibitor Tepotinib in Asian patients with aHCC, showing improved time to progression and better tolerability compared to sorafenib.
BRITISH JOURNAL OF CANCER
(2021)
Article
Cell Biology
Chu-Yen Chien, Ying-Chen Chen, Chia-Chen Hsu, Yu-Ting Chou, Shine-Gwo Shiah, Shyun-Yeu Liu, Alexander Cheng-Ting Hsieh, Ching-Yu Yen, Chien-Hsing Lee, Yi-Shing Shieh
Summary: Nicotine induces the expression of BiP in oral squamous cell carcinoma cells through the activation of the YAP-TEAD transcriptional complex, leading to increased malignancy. Inhibition of BiP expression can suppress nicotine-induced malignant behaviors, including epithelial-mesenchymal transition, migration, and invasion.
Review
Oncology
Shine-Gwo Shiah, Sung-Tau Chou, Jang-Yang Chang
Summary: Head and neck squamous cell carcinoma (HNSCC) is a common cancer arising from the oral epithelium, with high mortality rates despite improvements in diagnosis and treatment. Dysregulation of exosomes and metabolic abnormalities are involved in the development of HNSCC, suggesting potential therapeutic targets. MiRNAs play important roles in regulating HNSCC progression and may serve as non-invasive biomarkers for diagnosis and treatment.
Review
Oncology
Sung-Hsin Kuo, Kun-Huei Yeh, Chung-Wu Lin, Jyh-Ming Liou, Ming-Shiang Wu, Li-Tzong Chen, Ann-Lii Cheng
Summary: The prevalence of HP-negative gastric MALT lymphoma has increased, while HP-positive gastric MALT lymphoma has decreased. Some case studies have shown that a first-line HP eradication therapy (HPE)-like regimen can result in complete remission for some patients with localized HP-negative gastric MALT lymphoma. Previous sporadic reports have also indicated that some patients with extragastric MALT lymphoma can respond to antibiotic treatment.
Article
Oncology
Yu-Yun Shao, Pai-Sheng Chen, Liang-In Lin, Bin-Shyun Lee, Andrew Ling, Ann-Lii Cheng, Chiun Hsu, Da-Liang Ou
Summary: This study identified miR-10b-3p as a potential biomarker for predicting sorafenib efficacy in advanced HCC patients and confirmed its mechanism of action.
BRITISH JOURNAL OF CANCER
(2022)
Article
Oncology
Chi-Feng Tseng, Li-Tzong Chen, Horng-Dar Wang, Yi-Hong Liu, Shine-Gwo Shiah
Summary: The HOXB-AS3/EZH2 complex plays a significant role in causing sorafenib resistance and enhancing cancer stemness by epigenetically suppressing Dicer expression in liver cancer. These findings provide potential therapeutic strategies for diagnosing and treating liver cancer patients.
Article
Oncology
Kuo-Hsing Chen, Chia-Lang Hsu, Yu-Li Su, Chang-Tsu Yuan, Liang-In Lin, Jia-Huei Tsai, Yi-Hsin Liang, Ann-Lii Cheng, Kun-Huei Yeh
Summary: This study found that the immune contexture in the tumor microenvironment is closely associated with prognosis in patients with metastatic BRAF V600E mutant colorectal cancer. High expression of immune genes and complement activation are correlated with poor prognosis, and the complement score is strongly correlated with tumor-associated macrophage M2 signatures.
BRITISH JOURNAL OF CANCER
(2023)
Article
Gastroenterology & Hepatology
Masatoshi Kudo, Richard S. Finn, Shukui Qin, Kwang-Hyub Han, Kenji Ikeda, Ann-Lii Cheng, Arndt Vogel, Francesco Tovoli, Kazuomi Ueshima, Hiroshi Aikata, Carlos Lopez Lopez, Marc Pracht, Zhiqiang Meng, Bruno Daniele, Joong-Won Park, Daniel Palmer, Toshiyuki Tamai, Kenichi Saito, Corina E. Dutcus, Riccardo Lencioni
Summary: The study aimed to validate objective response as an independent predictor of overall survival (OS) in individuals with unresectable hepatocellular carcinoma (HCC) receiving systemic anti-angiogenic therapy. The results showed that objective response assessed by investigator-assessed mRECIST could predict the survival of patients. Further studies are needed to confirm this finding.
JOURNAL OF HEPATOLOGY
(2023)
Article
Oncology
Yu-Yun Shao, Hung-Wei Hsu, Rita Robin Wo, Han-Yu Wang, Ann-Lii Cheng, Chih-Hung Hsu
Summary: CDK9 inhibitors have been found to have potent anti-proliferative and apoptosis-inducing activities against HCC cells, while inhibiting downstream signaling molecules' phosphorylation. Animal experiments have confirmed the inhibitory effects of CDK9 inhibitors on HCC. Overexpression of CDK9 reduced the efficacy of CDK9 inhibitors, while knockdown of CDK9 expression reduced the proliferative activities of HCC cells.
Article
Gastroenterology & Hepatology
Chiao-Ling Tsai, Po-Sheng Yang, Feng-Ming Hsu, Ann-Lii Cheng, Wan-Ni Yu, Jason Chia-Hsien Cheng
Summary: This study investigated the effect of TOP1 inhibition and DNA-PKcs/RNF144A mechanism on radiosensitization mediated by natural killer (NK) cells in radiation therapy (RT). The results showed that TOP1 inhibitors and RT had a synergistic effect on hepatocellular carcinoma (HCC) cells, enhancing the anti-HCC effect of RT through increased DNA damage and DNA-PKcs signaling. RNF144A mediated DNA-PKcs ubiquitination and provided a reason for the difference in radiosensitization effect between HCC cells.
JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY
(2023)
Article
Oncology
Yu-Chieh Tsai, Tzu-Yin Wang, Chia-Lang Hsu, Wei-Chou Lin, Jyun-Yu Chen, Jia-Hua Li, Yeong-Shiau Pu, Ann-Lii Cheng, Jason Chia-Hsien Cheng, Sheng-Fang Su
Summary: This study found that inhibiting HDAC6 can enhance the radiosensitivity of bladder cancer and reduce the expression of genes related to cell migration, angiogenesis, and metastasis induced by radiotherapy, thereby improving therapeutic efficacy.
BRITISH JOURNAL OF CANCER
(2023)
Article
Oncology
Masatoshi Kudo, Richard S. Finn, Ann-Lii Cheng, Andrew X. Zhu, Michel Ducreux, Peter R. Galle, Naoya Sakamoto, Naoya Kato, Michitaka Nakano, Jing Jia, Arndt Vogel
Summary: This exploratory analysis examined the prognostic impact of baseline albumin-bilirubin (ALBI) score in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab + bevacizumab or sorafenib. The study found that atezolizumab + bevacizumab improved overall survival and progression-free survival compared to sorafenib in patients with ALBI score of 1, but not in patients with ALBI score of 2. ALBI grade appeared to be prognostic for outcomes in both treatment groups.
Article
Oncology
Philippe Merle, Masatoshi Kudo, Julien Edeline, Mohamed Bouattour, Ann-Lii Cheng, Stephen Lam Chan, Thomas Yau, Marcelo Garrido, Jennifer Knox, Bruno Daniele, Valeriy Breder, Ho Yeong Lim, Sadahisa Ogasawara, Stephane Cattan, Yee Chao, Abby B. Siegel, Ivan Martinez-Forero, Ziwen Wei, Chih-Chin Liu, Richard S. Finn
Summary: With extended follow-up, pembrolizumab demonstrated continued improvement in overall survival (OS) and progression-free survival (PFS) compared to placebo in advanced hepatocellular carcinoma (HCC) patients previously treated with sorafenib. The adverse event profile of pembrolizumab remained consistent with placebo.