Elevated <scp>BTG2</scp> improves the radiosensitivity of non‐small cell lung cancer (<scp>NSCLC</scp>) through apoptosis

Zhu, Changchun; Zhang, Songling; Xue, Aiying; Feng, Guoxing; Fan, Songqing

doi:10.1111/1759-7714.14410

Cited by 7 publications

(3 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…BTG2 can inhibit tumor growth and progression in breast cancer by suppressing the tumor microenvironments by regulating the mTORc2-AKT1-NFAT1-PHLPP2 signaling cascade [ 63 ]. In non-small cell lung cancer, BTG2 is a promising target for increasing radiation sensitivity with increased apoptosis and may be an early prognostic gene [ 64 ]. In transcriptomic analysis of mouse pancreatic tumor tissue, we identified BTG2 as a tumor suppressor gene whose expression was significantly induced by treatment with both T1-44 and Vactosertib in a mouse pancreatic tumor model.…”

Section: Discussionmentioning

confidence: 99%

Combination treatment of T1-44, a PRMT5 inhibitor with Vactosertib, an inhibitor of TGF-β signaling, inhibits invasion and prolongs survival in a mouse model of pancreatic tumors

Hong

Barczak

Park³

et al. 2023

Cell Death Dis

View full text Add to dashboard Cite

Pancreatic ductal adenocarcinoma (PDAC) is the most lethal type of cancer and the third leading cause of cancer death with the lowest 5-year survival rate. Heterogeneity, difficulty in diagnosis, and rapid metastatic progression are the causes of high mortality in pancreatic cancer. Recent studies have shown that Protein arginine methyltransferase 5 (PRMT5) is overexpressed in pancreatic cancers, and these patients have a worse prognosis. Recently, PRMT5 as an anti-cancer target has gained considerable interest. In this study, we investigated whether inhibition of PRMT5 activity was synergistic with blockade of TGF-β1 signaling, which plays an important role in the construction of the desmoplastic matrix in pancreatic cancer and induces therapeutic vulnerability. Compared with T1-44, a selective inhibitor of PRMT5 activity, the combination of T1-44 with the TGF-β1 signaling inhibitor Vactosertib significantly reduced tumor size and surrounding tissue invasion and significantly improved long-term survival. RNA sequencing analysis of mouse tumors revealed that the combination of T1-44 and Vactosertib significantly altered the expression of genes involved in cancer progression, such as cell migration, extracellular matrix, and apoptotic processes. In particular, the expression of Btg2, known as a tumor suppressor factor in various cancers, was markedly induced by combination treatment. Ectopic overexpression of Btg2 inhibited the EMT response, blocking cell migration, and promoted cancer cell death. These data demonstrate that the combination therapy of T1-44 with Vactosertib is synergistic for pancreatic cancer, suggesting that this novel combination therapy has value in the treatment strategy of patients with pancreatic cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Combination treatment of T1-44, a PRMT5 inhibitor with Vactosertib, an inhibitor of TGF-β signaling, inhibits invasion and prolongs survival in a mouse model of pancreatic tumors

Hong

Barczak

Park³

et al. 2023

Cell Death Dis

View full text Add to dashboard Cite

show abstract

“…And the DNA repair agent AV-153 plays an important role in DNA repair [26]. It has been shown that overexpression of BTG2 in lung cancer cells leads to an increase in the number of DDR-inducedc-H2AX lesions [27]. However, the efect of VRK1 on DDR has yet to be studied.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of VRK1 Inhibits Progression of Lung Squamous Cell Carcinoma through DNA Damage

Zhang

2023

Canadian Respiratory Journal

View full text Add to dashboard Cite

Background. Lung squamous cell carcinoma (LUSC) is a common malignancy. And the antitumor effect of bovine pox virus-associated kinase 1 (VRK1) is becoming a hot research topic. Methods. VRK1 expression and prognosis in LUSC were analyzed using the GEPIA database. The expression of VRK1 mRNA was detected in 25 LUSC clinical tissue samples by RT-PCR. VRK1 shRNA was transfected into LUSC NCI-H520 and SK-MES-1 cell lines to interfere with VRK1 expression, and the efficiency of VRK1 shRNA interference was detected by the western blot. The effects of VRK1 downregulation on LUSC cell viability, migration, cell cycle, and apoptosis were analyzed by the CCK8 assay, scratch assay, transwell assay, and flow cytometry. The effect of VRK1 downregulation on DNA damage response (DDR) was examined by immunofluorescence staining and western blot assays and further validated by in vivo experiments. Results. VRK1 was highly expressed in both LUSC tissues and cells. Survival analysis showed that the overall survival of LUSC patients with high VRK1 expression was significantly lower than that of LUSC patients with low VRK1 expression ( P = 0.0026 ). The expression level of the VRK1 gene was significantly higher in cancer tissues of LUSC patients than in paracancerous tissues. After transfection of VRK1 shRNA in both LUSC cells, cell activity decreased ( P < 0.001 ), migration ability started to be inhibited ( P < 0.001 ), the ratio of G0/G1 phase cells increased ( P < 0.001 ), and apoptosis rate increased ( P < 0.001 ). Immunofluorescence and western blot results showed that shVRK1 increased the level of γ-H2A.X ( P < 0.001 ) and promoted apoptosis of tumor cells ( P < 0.001 ). In addition, the results of animal experiments showed that shVRK1 had antitumor effects ( P < 0.001 ) and a combined effect with DOX ( P < 0.001 ). Conclusion. The downregulation of VRK1 significantly affected the proliferation, apoptosis, migration, and cell cycle progression of LUSC cells via DDR, suggesting that VRK1 is a suitable target for potential LUSC therapy.

show abstract

“…Its expression can be activated by P53, leading to the inhibition of the cell cycle process [19]. In addition, BTG2 was also involved in many biological processes such as cell senescence [20], cell differentiation [21], oxidative damage [22] and DNA damage repair [23]. Then, what role does BTG2 play in the muscles?…”

Section: Introductionmentioning

confidence: 99%

miR-103-3p Regulates the Proliferation and Differentiation of C2C12 Myoblasts by Targeting BTG2

He,

Yang,

Yuan

et al. 2023

IJMS

View full text Add to dashboard Cite

Skeletal muscle, a vital and intricate organ, plays a pivotal role in maintaining overall body metabolism, facilitating movement, and supporting normal daily activities. An accumulating body of evidence suggests that microRNA (miRNA) holds a crucial role in orchestrating skeletal muscle growth. Therefore, the primary aim of this study was to investigate the influence of miR-103-3p on myogenesis. In our study, the overexpression of miR-103-3p was found to stimulate proliferation while suppressing differentiation in C2C12 myoblasts. Conversely, the inhibition of miR-103-3p expression yielded contrasting effects. Through bioinformatics analysis, potential binding sites of miR-103-3p with the 3’UTR region of BTG anti-proliferative factor 2 (BTG2) were predicted. Subsequently, dual luciferase assays conclusively demonstrated BTG2 as the direct target gene of miR-103-3p. Further investigation into the role of BTG2 in C2C12 myoblasts unveiled that its overexpression impeded proliferation and encouraged differentiation in these cells. Notably, co-transfection experiments showcased that the overexpression of BTG2 could counteract the effects induced by miR-103-3p. In summary, our findings elucidate that miR-103-3p promotes proliferation while inhibiting differentiation in C2C12 myoblasts by targeting BTG2.

show abstract

Elevated BTG2 improves the radiosensitivity of non‐small cell lung cancer (NSCLC) through apoptosis

Cited by 7 publications

References 33 publications

Combination treatment of T1-44, a PRMT5 inhibitor with Vactosertib, an inhibitor of TGF-β signaling, inhibits invasion and prolongs survival in a mouse model of pancreatic tumors

Combination treatment of T1-44, a PRMT5 inhibitor with Vactosertib, an inhibitor of TGF-β signaling, inhibits invasion and prolongs survival in a mouse model of pancreatic tumors

Downregulation of VRK1 Inhibits Progression of Lung Squamous Cell Carcinoma through DNA Damage

miR-103-3p Regulates the Proliferation and Differentiation of C2C12 Myoblasts by Targeting BTG2

Contact Info

Product

Resources

About