A New Long Noncoding RNA ALB Regulates Autophagy by Enhancing the Transformation of LC3BI to LC3BII during Human Lens Development

Abstract

Autophagy is essential in lens organelle degradation. This study aimed to seek potential autophagy-associated long noncoding RNAs (lncRNAs) and their relative mechanisms in human lens development using the “fried egg” lentoid body (LB) generation system. The expression pattern of LC3B in differentiating LBs was similar to that in developing a mouse lens in vivo. Among the massive lncRNAs expressed with a significant difference between induced pluripotent stem cells (iPSCs) and LBs, lncRNA affecting LC3B (ALB), which was predicted to have a co-relationship with the autophagy marker LC3B, was highly expressed in differentiating lens fibers in LBs. This result was consistent with its high expression in human embryonic lenses compared to those in embryonic stem cells (ESCs). Furthermore, lncRNA ALB knockdown resulted in the downregulation of LC3BII at the protein level, therefore inhibiting the autophagy process in human lens epithelial cells (HLECs). Our results identify lncRNA ALB, a potential autophagy regulator in organelle degradation during human lens development, highlighting the importance of lncRNAs in lens development.

Opacification of lentoid bodies derived from human induced pluripotent stem cells is accelerated by hydrogen peroxide and involves protein aggregation

“…Previous studies have indicated that autophagy may play an important role in both lens development and cataract formation (Andley & Goldman, ; Chen et al, ; Morishita et al, ; Sagona, Nezis, & Stenmark, ; Wignes, Goldman, Weihl, Bartley, & Andley, ). Our previous study on this topic found that autophagy was involved in the differentiation process of LBs (Fu et al, ), which is partially consistent with its function in human lens development. To investigate the role of autophagy in ARCs as well as the clouding process of LBs, we analyzed the expression of autophagy marker LC3B in both human lens capsules from ARC patients and in LBs at different time points.…”

“…To address this gap, our group recently developed a new lens regeneration method-we have termed it the "fried egg" methodduring which LBs derived from human iPSCs showed transparent morphology and not only expressed lens-specific markers but also exhibited basic optic characteristics (Fu et al, 2017a). Moreover, the LB differentiation process partially mimicked human lens development (Fu et al, 2017a;Fu et al, 2017b). Therefore, we assume that LBs differentiated from iPSCs or ESCs using the "fried egg" method may also have the potential capacity in ARC disease model development.…”

LncRNA CASC15 promotes colon cancer cell proliferation and metastasis by regulating the miR‑4310/LGR5/Wnt/β‑catenin signaling pathway

“…Long noncoding RNAs (lncRNAs) are a member of noncoding RNA and possess a length of over 200 nucleotides, but have no protein-coding potential (5)(6)(7)(8). Many studies show that lncRNA has widely functions in a diversity of biological processes, such as development, cell proliferation, apoptosis and mobility (9)(10)(11)(12)(13). LncRNA has been demonstrated to be involved in the development and progression of various cancers (14).…”

Hypoxia‐sensitive LINC01436 is regulated by E2F6 and acts as an oncogene by targeting miR‐30a‐3p in non‐small cell lung cancer

“…Long noncoding RNA (lncRNA) have been shown to contribute to cancerous phenotypes such as proliferation, growth suppression, motility, immortality, angiogenesis and viability (Fu et al ., ; Lin et al ., ; Schmitt and Chang, ). Evidence has indicated that lncRNA function primarily through their interactions with cellular macromolecules such as protein, DNA or RNA (Fang et al ., ; Schmitt and Chang, ; Sun et al ., ; Zhang et al ., ).…”