Pseudogene MSTO2P Interacts with miR-128-3p to Regulate Coptisine Sensitivity of Non-Small-Cell Lung Cancer (NSCLC) through TGF-β Signaling and VEGFC

Abstract

Background. Coptisine has been widely used for treating a variety of cancer types. To date, whether pseudogene is implicated in coptisine resistance of NSCLC remains unknown. Methods. We performed MTT to assess the cell viability of A549 and Calu-1 cells. The transwell assay was used to examine the invasion of cells. TUNEL was used to determine apoptosis. Results. Our data showed that coptisine treatment suppressed cell viability and invasion of NSCLC cells while contributing to apoptosis. MiR-128-3p negatively regulated MSTO2P. miR-128-3p reverted MSTO2P knockdown-attenuated cell viability and invasion, as well as promoted cell apoptosis of A549 cells. Moreover, we identified TGF-β signaling and VEGFC as key downstream effectors for MSTO2P and miR-128-3p in A549 cells. MiR-128-3p mimic inhibited TGF-β pathway-associated genes (TGFBR1, Smad2, Smad5, and Smad9), whereas miR-128-3p inhibitor exerted opposite effect. MSTO2P knockdown led to attenuated expression levels of TGFBR1, Smad2, Smad5 and Smad9. VEGFC overexpression greatly rescued miR-128-3p-modulated cell viability, invasion, and apoptosis of A549 cells. Conclusion. MSTO2P plays a role in coptisine therapy of NSCLC through miR-128-3p. The findings will advance our understanding of NSCLC treatment.

Magnetic Graphene Oxide Nanocomposites Boosts Craniomaxillofacial Bone Regeneration by Modulating circAars/miR-128-3p/SMAD5 Signaling Axis

“… 28 miR-128-3p mimic could significantly influence the expression of SMAD2, SMAD5 and SMAD9 in non-small cell lung cancer A549 cell line. 29 To determine whether SMAD5 is a direct binding gene of miR-128-3p, the miR-128-3p inhibitor or mimic was transfected in cells containing MUT sequence and the WT sequence of SMAD5 through a luciferase reporter assay. It revealed that miR-128-3p inhibitor significantly increased the luciferase intensity and miR-128-3p mimic significantly decreased the luciferase intensity of SMAD5-WT when those were compared with the control group; however, no significant effect was found on the luciferase intensity of SMAD5-MUT ( Figure 7A and B ).…”

“…However, miR-128-3p inhibitor significantly promoted the expression of SMAD2, SMAD5 and SMAD9. 29 However, whether miR-128-3p could regulate MGO nanocomposites mediated BMSCs osteogenic behaviors via regulating SMAD5 has not been fully clarified. Interestingly, we found that circAars overexpression could positively improve SMAD5 activity and the miR-128-3p negatively manage the level of SMAD5.…”

Inferring pseudogene–MiRNA associations based on an ensemble learning framework with similarity kernel fusion

“…Pseudogene MSTO2P is found to be implicated in several diseases including lung cancer 32 , colorectal cancer 33 , etc. MSTO2P could function as a miR-128-3p sponge in non-small cell lung cancer cells (NSCLC), and MSTO2P /miR-128-3p to regulate coptisine sensitivity of NSCLC cells via TGF- β pathway.…”

TGF-?/FAK/AKT Signal Pathway Blocked by Astragaloside, Hinders the Invasion and Metastasis of Non-Small Cell Lung Cancer

“…EMT occurs mainly in various physiological and pathological processes, including tissue and embryonic development, organ injury and repair, organ fibrosis, metastasis of cancerous tumors, and other events. The pathway controls various cellular processes, such as cell specialization, programmed cell death, and cell growth, and has been demonstrated to hinder or facilitate the advancement of tumors through various mechanisms [16] . Dysfunction or atypical stimulation of TGF-β may result in various pathological disorders, such as cancerous growths, fibrotic ailments, aberrant immune reactions, and more.…”