Hedgehog signaling and its molecular perspective with cholesterol: a comprehensive review

Kaushal, Jyoti; Batra, Surinder K.; Rachagani, Satyanarayana

doi:10.1007/s00018-022-04233-1

Cited by 16 publications

(19 citation statements)

References 212 publications

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“…18 The cholesterol efflux and modulates are influenced by Patched1 (Ptch1) which is another membrane receptor of Hh signaling. 19 The crystal structure of human SMO in complex with cholesterol shows the 3b-hydroxyl group of cholesterol forms a noncovalent hydrogen bond with residue Asp95, and this point has been also mentioned in the subsequent research reports. 20,21 In contrast, some studies have pointed out that SMO is covalently modified by cholesterol and the 3b-hydroxyl group of cholesterol forms a covalent bond with the carboxyl group of residue Asp95.…”

Section: Introductionmentioning

confidence: 70%

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Studying noncovalent or covalent bond problem between smoothened and cholesterol by molecular dynamics simulation and Markov state model

Feng

Sánchez

Bai

2022

Phys. Chem. Chem. Phys.

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Section: Introductionmentioning

confidence: 70%

“…18 The cholesterol efflux and modulates are influenced by Patched1 (Ptch1) which is another membrane receptor of Hh signaling. 19…”

Section: Introductionmentioning

confidence: 99%

Studying noncovalent or covalent bond problem between smoothened and cholesterol by molecular dynamics simulation and Markov state model

Feng

Sánchez

Bai

2022

Phys. Chem. Chem. Phys.

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“…The IFT machinery shuttles SuFu, GLI and GLI R proteins from the ciliary tip to the cell body and vice versa. GLI R enters the nucleus where represses the expression of genes under Hh control (Figure 2A) (80)(81)(82).…”

Section: The Hedgehog Signaling Pathwaymentioning

confidence: 99%

“…By contrast, binding of ligand (Hh) to PTCH1 leads to the formation of oligomers, which are moved out of the cilium and degraded in endosomes (83). This alleviates SMO repression causing its re-localization to the cilium, where switches off GLI processing by interacting with SuFu, leading to the activation of GLI (GLI A ) (80)(81)(82). GLI A is shuttle back to the nucleus allowing transcription of genes under Hh control.…”

Section: The Hedgehog Signaling Pathwaymentioning

confidence: 99%

Primary Cilia in Pancreatic β- and α-Cells: Time to Revisit the Role of Insulin-Degrading Enzyme

et al. 2022

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The primary cilium is a narrow organelle located at the surface of the cell in contact with the extracellular environment. Once underappreciated, now is thought to efficiently sense external environmental cues and mediate cell-to-cell communication, because many receptors, ion channels, and signaling molecules are highly or differentially expressed in primary cilium. Rare genetic disorders that affect cilia integrity and function, such as Bardet-Biedl syndrome and Alström syndrome, have awoken interest in studying the biology of cilium. In this review, we discuss recent evidence suggesting emerging roles of primary cilium and cilia-mediated signaling pathways in the regulation of pancreatic β- and α-cell functions, and its implications in regulating glucose homeostasis.

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“…GLI1 and GLI2, key molecules in the HHSP, have been reported to play important roles in maintaining the stemness of GC cells [35][36][37][38] . Therefore, we wondered whether abnormally expressed miR-378a-3p might inhibit GLI1/2 expression and further influence the stemness of GC cells.…”

Section: Mir-378a-3p Inhibits Gli1/2 Expression and Further Inhibits ...mentioning

confidence: 99%

MiR-378a-3p acts as a tumor suppressor in gastric cancer via directly targeting RAB31 and inhibiting the Hedgehog pathway proteins GLI1/2

Liu

et al. 2022

Cancer Biol Med

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Objective: To improve the prognosis of patients with gastric cancer (GC), more effective therapeutic targets are urgently needed. Increasing evidence indicates that miRNAs are involved in the progression of various tumors, and RAS-associated protein in the brain 31 (RAB31) is upregulated and promotes the progression of multiple malignant tumors. Here, we focused on identifying RAB31-targeted miRNAs and elucidating their potential mechanism in the progression of GC. Methods: RAB31 and miR-378a-3p expression levels were detected in paired fresh GC tissues and GC cell lines. Bioinformatics analysis was used to predict the miRNAs targeting RAB31 and the relationships between RAB31 and other genes. Dual-luciferase reporter assays were applied to verify the targeted interaction relationship. CCK-8, colony formation, flow cytometry, wound healing, and Transwell assays were performed to assess the proliferation, apoptosis, migration, and invasion of GC cells. Tumorsphere formation assays were performed to assess the stemness of gastric cancer stem cells. Related proteins were detected by Western blot. Xenograft assays in nude mice were performed to explore the effect of miR-378a-3p in vivo. Results: We report the first evidence that miR-378a-3p is downregulated in GC, whereas its overexpression inhibits proliferation, invasion, and migration as well as promotes apoptosis in GC cells. Mechanistically, miR-378a-3p inhibits the progression of GC by directly targeting RAB31. Restoring RAB31 expression partially offsets the inhibitory effect of miR-378a-3p. Further research revealed that miR-378a-3p inhibits GLI1/2 in the Hedgehog signaling pathway and attenuates the stemness of gastric cancer stem cells. Finally, xenograft assays showed that miR-378a-3p inhibits GC tumorigenesis in vivo. Conclusions: MiR-378a-3p inhibits GC progression by directly targeting RAB31 and inhibiting the Hedgehog signaling pathway proteins GLI1/2.

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Hedgehog signaling and its molecular perspective with cholesterol: a comprehensive review

Cited by 16 publications

References 212 publications

Studying noncovalent or covalent bond problem between smoothened and cholesterol by molecular dynamics simulation and Markov state model

Studying noncovalent or covalent bond problem between smoothened and cholesterol by molecular dynamics simulation and Markov state model

Primary Cilia in Pancreatic β- and α-Cells: Time to Revisit the Role of Insulin-Degrading Enzyme

MiR-378a-3p acts as a tumor suppressor in gastric cancer via directly targeting RAB31 and inhibiting the Hedgehog pathway proteins GLI1/2

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