91猫先生

研究主题

(一)&苍产蝉辫;&苍产蝉辫; 研究DEAD-box RNA解旋酶DDX3的生物功能

人类DDX3蛋白是DEAD-box RNA解旋酶家族成员之一，这些RNA解旋酶在真核生物的基因表现与调控扮演不可或缺的角色。先前，我们证明DDX3对於具有较长及二级结构5’ UTR的特定mRNA转译至关重要。因為DDX3在执行转译功能时需要其RNA解旋酶活性，所以我们认為DDX3可能在转译初期藉由解开特定mRNA的5’ UTR二级结构来促进核糖体扫描。研究DDX3介导转译调控的生物功能非常有趣。然而，目前还有一些尚未清楚解答的问题如下：

(1)   DDX3在microRNA生合成及RNA干扰所扮演的角色

(2)   DDX3在卵子发生和女性生育能力中的重要性

(3)   DDX3对於神经元和脑部发育的影响

(4)   DDX3可能与神经退化性疾病有关

(二)&苍产蝉辫;&苍产蝉辫; 探讨大肠癌细胞在缺氧下的转译调控机制

大肠直肠癌（CRC）是全球最常见的癌症之一。在台湾，大肠直肠癌已连续15年位居癌症发生率首位。许多大肠直肠癌末期患者常因治疗无效而在五年内死亡。因此，亟需新的策略和改进的疗法来治疗大肠直肠癌。缺氧是普遍常见的生理及病理现象，包括肿瘤生成。缺氧可能促进肿瘤恶化并与预后不良有关。因此，深入了解缺氧所导致基因表现的变化，可能开啟未来在癌症治疗上的新视野。我们目前的研究主要集中在以下问题：

(1)   在大肠癌细胞中研究缺氧诱导转译的分子机制

(2)   鑑定在缺氧下活化特定mRNA转译的RNA结合蛋白

(3)   尋找大肠直肠癌的診斷生物標記和潛在的抗癌標靶

(叁)&苍产蝉辫;&苍产蝉辫; 提高中国仓鼠卵巢细胞生产重组蛋白的能力

值得注意的是，將近八成核准使用的人类治療抗體是由中國倉鼠卵巢(CHO)细胞所产生。為了提高CHO细胞重组蛋白的产量并且降低细胞培养成本，我们计划利用基因工程技术来改良CHO细胞株。

发表着作

1.      Hung-Hsuan Li, Hsin-Yuan Hung, Jau-Song Yu, Ming-Chih Lai*. (2024 Dec). Hypoxia-induced translation of collagen-modifying enzymes PLOD2 and P4HA1 is dependent on RBM4 and eIF4E2 in human colon cancer HCT116 cells. FEBS J. (SCI, 2023 IF= 5.5, Ranking 58/313 in BIOCHEMISTRY & MOLECULAR BIOLOGY)

2.      Shang-Yu Tsai, Chih-Hung Lin, Yu-Ting Jiang, Guo-Jen Huang, Haiwei Pi, Hsin-Yuan Hung, Woan-Yuh Tarn, Ming-Chih Lai*. (2024 Nov). DDX3 is critical for female fertility via translational control in oogenesis. Cell Death Discovery 10(1):472. (SCI, 2023 IF= 6.1, Ranking 49/205 in CELL BIOLOGY)

3.      Ming-Chih Lai^*, Yen-Ling Yu, Chiao-Nung Chen, Jau-Song Yu, Hsin-Yuan Hung, Shih-Peng Chan^*. (2024 Nov). DDX3 participates in miRNA biogenesis and RNA interference through translational control of PACT and interaction with AGO2. FEBS Open Bio doi: 10.1002/2211-5463.13920. (SCI, 2023 IF= 2.8, Ranking 184/313 in BIOCHEMISTRY & MOLECULAR BIOLOGY)

4.      Ming-Chih Lai*, Yi-Pin Chen, Ding-An Li, Jau-Song Yu, Hsin-Yuan Hung, Woan-Yuh Tarn* (2022 Feb) DDX3 interacts with USP9X and participates in deubiquitination of the anti-apoptotic protein MCL1. FEBS J. 289(4): 1043-1061. (SCI, 2023 IF= 5.5, Ranking 58/313 in BIOCHEMISTRY & MOLECULAR BIOLOGY)

5.      Ming-Chih Lai, Han-Hsiang Chen, Peng Xu, Robert YL Wang*. (2020 Jan). Translation control of Enterovirus A71 gene expression. Journal of Biomedical Science 27(1):22. (SCI, 2023 IF= 9.0 Ranking 30/205 in CELL BIOLOGY)

6.      Tsung-Ming Chen, Ming-Chih Lai, Yi-Han Li, Ya-Ling Chan, Chih-Hao Wu, Yu-Ming Wang, Chun-Wei Chien, San-Yuan Huang, H. Sunny Sun*, Shaw-Jenq Tsai*. (2019 Mar). hnRNPM induces translation switch under hypoxia to promote colon cancer development. EBioMedicine 41: 299-309. (SCI, 2023 IF= 9.7, Ranking 12/189 in MEDICINE, RESEARCH & EXPERIMENTAL)

7.      Yu-Chang Ku, Min-Hua Lai, Chen-Chia Lo, Yi-Chuan Cheng, Jian-Tai Qiu, Woan-Yuh Tarn, Ming-Chih Lai*. (2018 Dec). DDX3 participates in translational control of inflammation induced by infections and injuries. Mol. Cell. Biol. 39(1): e00285-18. (SCI, 2023 IF= 3.2, Ranking 155/313 in BIOCHEMISTRY & MOLECULAR BIOLOGY)

8.      Jeng-Ting Chen, Chien-Chun Liu, Jau-Song Yu, Hung-Hsuan Li, Ming-Chih Lai*. (2018 Sep). Integrated omics profiling identifies hypoxia-regulated genes in HCT116 colon cancer cells. J. Proteomics 188: 139-151. (SCI, 2023 IF= 2.8, Ranking 35/85 in BIOCHEMICAL RESEARCH METHODS)

9.      Ming-Chih Lai*, Chiao-May Chang, H. Sunny Sun*. (2016 Apr). Hypoxia induces autophagy through translational up-regulation of lysosomal proteins in human colon cancer cells. PLOS ONE 11(4): e0153627. (SCI, 2023 IF= 2.9, Ranking 31/134 in MULTIDISCIPLINARY SCIENCES)

10.  Ming-Chih Lai*, H. Sunny Sun, Shainn-Wei Wang, Woan-Yuh Tarn*. (2016 Jan). DDX3 functions in antiviral innate immunity through translational control of PACT. FEBS J. 283(1): 88-101. (SCI, 2023 IF= 5.5, Ranking 58/313 in BIOCHEMISTRY & MOLECULAR BIOLOGY)

11.  Tsung-Ming Chen, Yu-Heng Shih, Joseph T. Tseng, Ming-Chih Lai, Chih-Hao Wu, Yi-Han Li, Shaw-Jenq Tsai*, H. Sunny Sun*. (2014 Mar). Overexpression of FGF9 incolon cancer cells is mediated by hypoxia-induced translational activation. Nucleic Acids Res. 42(5): 2932-2944. (SCI, 2023 IF= 16.6, Ranking 6/313 in BIOCHEMISTRY & MOLECULAR BIOLOGY)

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