Induced Pluripotent Stem Cell Technology: Trends in Molecular Biology, from Genetics to Epigenetics

The authors reviewed the molecular basis of reprogramming, including the reprogramming factors, applied vectors and epigenetic modifications to provide a comprehensive guide for reprogramming studies.
[Epigenomics]
Maali, A., Maroufi, F., Sadeghi, F., Atashi, A., Kouchaki, R., Moghadami, M., & Azad, M. (2021). Induced pluripotent stem cell technology: trends in molecular biology, from genetics to epigenetics. Epigenomics. https://doi.org/10.2217/epi-2020-0409 Cite
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MiR-142-3p Targets HMGA2 and Suppresses Breast Cancer Malignanc

The authors demonstrated that the miRNA miR-142-3p directly targeted the 3′ untranslated region of HMGA2, which encoded an onco-embryonic protein that was overexpressed in most cancers, including breast cancer.
[Life Sciences]
Mansoori, B., Duijf, P. H. G., Mohammadi, A., Safarzadeh, E., Ditzel, H. J., Gjerstorff, M. F., Cho, W. C.-S., & Baradaran, B. (2021). MiR-142-3p targets HMGA2 and suppresses breast cancer malignancy. Life Sciences, 119431. https://doi.org/10.1016/j.lfs.2021.119431 Cite
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YBX1 Is Required for Maintaining Myeloid Leukemia Cell Survival by Regulating BCL2 Stability in an m6A-Dependent Manner

Investigators showed that YBX1 was specifically required for maintaining myeloid leukemia cell survival in an m6A-dependent manner.
[Blood]
Feng, M., Xie, X., Han, G., Zhang, T., Li, Y., Li, Y., Yin, R., Wang, Q., Zhang, T., Wang, P., Hu, J., Cheng, Y., Gao, Z., Wang, J., Chang, J., Cui, M., Gao, K., Chai, J., Liu, W., … Zhang, H. (2021). YBX1 is required for maintaining myeloid leukemia cell survival by regulating BCL2 stability in an m6A-dependent manner. Blood, blood.2020009676. https://doi.org/10.1182/blood.2020009676 Cite
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The Oncogene AAMDC Links PI3K-AKT-mTOR Signaling with Metabolic Reprograming in Estrogen Receptor-Positive Breast Cancer

Scientists uncovered that Adipogenesis associated Mth938 domain containing (AAMDC) regulates the expression of several metabolic enzymes involved in the one-carbon folate and methionine cycles, and lipid metabolism.
[Nature Communications]
Golden, E., Rashwan, R., Woodward, E. A., Sgro, A., Wang, E., Sorolla, A., Waryah, C., Tie, W. J., Cuyàs, E., Ratajska, M., Kardaś, I., Kozlowski, P., Johnstone, E. K. M., See, H. B., Duffy, C., Parry, J., Lagerborg, K. A., Czapiewski, P., Menendez, J. A., … Blancafort, P. (2021). The oncogene AAMDC links PI3K-AKT-mTOR signaling with metabolic reprograming in estrogen receptor-positive breast cancer. Nature Communications, 12(1), 1920. https://doi.org/10.1038/s41467-021-22101-7 Cite
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SWATH-MS Proteomics of PANC-1 and MIA PaCa-2 Pancreatic Cancer Cells Allows Identification of Drug Targets Alternative to MEK and PI3K Inhibition

Scientists compared PANC-1 and MIA PaCa-2 pancreatic cancer cells which are, respectively, resistant and sensitive to MEK- and PI3K-targeted therapy.
[Biochemical and Biophysical Research Communications]
Aguilar-Valdés, A., Noriega, L. G., Tovar, A. R., Ibarra-Sánchez, M. de J., Sosa-Hernández, V. A., Maravillas-Montero, J. L., & Martínez-Aguilar, J. (2021). SWATH-MS proteomics of PANC-1 and MIA PaCa-2 pancreatic cancer cells allows identification of drug targets alternative to MEK and PI3K inhibition. Biochemical and Biophysical Research Communications, 552, 23–29. https://doi.org/10.1016/j.bbrc.2021.03.018 Cite
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Dysregulation of miR-23b-5p Promotes Cell Proliferation via Targeting FOXM1 in Hepatocellular Carcinoma

Gain- or loss-of-function assays demonstrated that miR-23b-5p induced G0/G1 cell cycle arrest and inhibited cell proliferation both in vitro and in vivo. qRT-PCR, western blot and luciferase assays verified that Mammalian transcription factor Forkhead Box M1 (FOXM1), upregulated in hepatocellular carcinoma specimens, was negatively correlated with miR-23b-5p expression and acted as a direct downstream target of miR-23b-5p.
[Cell Death Discovery]
Dysregulation of miR-23b-5p promotes cell proliferation via targeting FOXM1 in hepatocellular carcinoma | Cell Death Discovery. (n.d.). Retrieved March 19, 2021, from https://www.nature.com/articles/s41420-021-00440-0 Cite
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CRISPRi Screens Reveal a DNA Methylation-Mediated 3D Genome Dependent Causal Mechanism in Prostate Cancer

Scientists performed CRISPRi screens of 260 cis-regulatory elements (rCREs) in prostate cancer cell lines. They found that rCREs harboring high risk SNPs were more essential for cell proliferation and H3K27ac occupancy was a strong indicator of essentiality.
[Nature Communications]
Ahmed, M., Soares, F., Xia, J.-H., Yang, Y., Li, J., Guo, H., Su, P., Tian, Y., Lee, H. J., Wang, M., Akhtar, N., Houlahan, K. E., Bosch, A., Zhou, S., Mazrooei, P., Hua, J. T., Chen, S., Petricca, J., Zeng, Y., … He, H. H. (2021). CRISPRi screens reveal a DNA methylation-mediated 3D genome dependent causal mechanism in prostate cancer. Nature Communications, 12(1), 1781. https://doi.org/10.1038/s41467-021-21867-0 Cite
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p97/VCP Is Highly Expressed in the Stem-Like Cells of Breast Cancer and Controls Cancer Stemness Partly through the Unfolded Protein Response

Researchers examined p97 expression in the stem-like cancer cells or cancer stem cells (CSCs), a cell population that purportedly underscores cancer initiation, therapeutic resistance, and recurrence.
[Cell Death & Disease]
Li, C., Huang, Y., Fan, Q., Quan, H., Dong, Y., Nie, M., Wang, J., Xie, F., Ji, J., Zhou, L., Zheng, Z., & Wang, L. (2021). p97/VCP is highly expressed in the stem-like cells of breast cancer and controls cancer stemness partly through the unfolded protein response. Cell Death & Disease, 12(4), 1–16. https://doi.org/10.1038/s41419-021-03555-5 Cite
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Frondoside A Inhibits a MYC-driven Medulloblastoma Model Derived from Human Induced Pluripotent Stem Cells.

Scientists applied a synthetic mRNA-driven strategy to generate neuronal precursors from hiPSCs. These neuronal precursors were transformed by the MYC oncogene combined with p53 loss-of-function to establish a MYC-driven medulloblastoma model recapitulating the histological and transcriptomic hallmarks of Group 3 MB.
[Molecular Cancer Therapeutics]
Frondoside A Inhibits a MYC-driven Medulloblastoma Model Derived from Human Induced Pluripotent Stem Cells. | Molecular Cancer Therapeutics. (n.d.). Retrieved March 17, 2021, from https://mct.aacrjournals.org/content/early/2021/03/15/1535-7163.MCT-20-0603.long Cite
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CDK8 Maintains Stemness and Tumorigenicity of Glioma Stem Cells by Regulating the C-MYC Pathway

Investigators demonstrated how cyclin-dependent kinase 8 (CDK8) played an essential role in maintaining stemness and tumorigenicity in glioma stem cells.
[Oncogene]
Fukasawa, K., Kadota, T., Horie, T., Tokumura, K., Terada, R., Kitaguchi, Y., Park, G., Ochiai, S., Iwahashi, S., Okayama, Y., Hiraiwa, M., Yamada, T., Iezaki, T., Kaneda, K., Yamamoto, M., Kitao, T., Shirahase, H., Hazawa, M., Wong, R. W., … Hinoi, E. (2021). CDK8 maintains stemness and tumorigenicity of glioma stem cells by regulating the c-MYC pathway. Oncogene, 1–13. https://doi.org/10.1038/s41388-021-01745-1 Cite
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Overexpression of Annexin A2 Promotes Proliferation by Forming a Glypican 1/C-Myc Positive Feedback Loop: Prognostic Significance in Human Glioma

Researchers found that Annexin A2 (ANXA2)-induced glioma cell proliferation in a c-Myc-dependent manner. ANXA2 increased the expression of Glypican 1 (GPC1) via c-Myc and the upregulated GPC1 further promoted the c-Myc level, forming a positive feedback loop, which led to enhanced proliferation of glioma cells.
[Cell Death & Disease]
Li, X., Nie, S., Lv, Z., Ma, L., Song, Y., Hu, Z., Hu, X., Liu, Z., Zhou, G., Dai, Z., Song, T., Liu, J., & Wang, S. (2021). Overexpression of Annexin A2 promotes proliferation by forming a Glypican 1/c-Myc positive feedback loop: prognostic significance in human glioma. Cell Death & Disease, 12(3), 1–13. https://doi.org/10.1038/s41419-021-03547-5 Cite
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