Retracted: MicroRNA let‐7b Inhibits Proliferation and Induces Apoptosis of Castration‐Resistant Prostate Cancer Cells by Blocking the Ras/Rho Signaling Pathway via NRAS

Abstract

Castration-resistant prostate cancer (CRPC) is a heterogeneous disease with a high mortality rate. MicroRNA let-7b has been documented to act as a tumor suppressor in various cancers. The present study intends to explore how let-7b affects CRPC by influencing the Ras/Rho signaling pathway. The expression of neuroblastoma RAS viral oncogene homolog (NRAS) and let-7b in CRPC tissues and cells was determined. The binding relationship between let-7b and NRAS was predicted by the Targetscan website and verified by the dual luciferase reporter gene assay. Gain-of-function and loss-of-function approaches were used to investigate the relationship among let-7b, NRAS, and Ras/Rho signaling pathway as well as their effects on the proliferation, invasion, and apoptosis of CRPC cells. The tumor formation ability of nude mice was tested in vivo. Poorly expressed Let-7b and highly expressed NRAS were presented in CRPC tissues and androgen-independent cell line C4-2. NRAS was verified as a target gene of let-7b. Overexpression of let-7b or silencing of NRAS repressed C4-2 cell proliferation and invasion in vitro and tumor growth in vivo as well as induced C4-2 cell apoptosis in vitro through the blockage of the Ras/Rho signaling pathway. Let-7b overexpression or NRAS silencing reduced matrix metalloproteinase-2, matrix metalloproteinase-9, Bcl-2, cyclinD1, and CyclinB expression, but elevated Caspase3 expression in vivo and in vitro. Taken together, in CRPC, let-7b blocks the Ras/Rho signaling pathway by inhibiting NRAS expression, thereby inhibiting cell proliferation and invasion, and promoting cell apoptosis. Thus, let-7b targeting NRAS may be a potential therapeutic target for the repression of CRPC.Prostate cancer is a kind of noncutaneous cancer with the highest morbidity and the second highest mortality among men. 1 In recent years, advanced and metastatic prostate cancer have become a heavy burden that cannot be solved in short term in the healthcare system. 2 For metastatic prostate cancer, patients can only receive temporary disease control measures by blockading or castrating androgen. 3 Usually, prostate cancer may develop into a lethal form of castration-resistant prostate cancer (CRPC) within 2-3 years as the majority of patients resist to the treatment. 4 CRPC is historically considered as a kind of chemoresistant tumor with a palliative treatment only lasting 1-2 years. 5 It is a major challenge in the treatment of CRPC for lacking easily available and reliable biomarkers. 6 For the same, we conducted a series of experiments in the present study to explore new targets for CRPC treatment.Let-7b belongs to the microRNA let-7 family and usually acts as a tumor suppressor in different types of

Aberrant Methylation and Differential Expression of SLC2A1, TNS4, GAPDH, ATP8A2, and CASZ1 Are Associated with the Prognosis of Lung Adenocarcinoma

“…Cell adhesion molecules are closely related to the invasion and migration of multiple tumors [ 33 – 35 ]. The Ras gene is abnormally expressed in gastric cancer [ 36 ], prostate cancer [ 37 ], and colorectal cancer [ 38 ], and it is associated with epithelial-mesenchymal transition (EMT) and drug resistance of cancer. These evidences suggest that the DGs Hyper and the UGs Hypo may play an important regulatory role in the molecular mechanism of LUAD.…”

MicroRNA as an Important Target for Anticancer Drug Development

“…The analysis of 21 patients with different types of tumor showed that the expression of let-7 decreased significantly in twelve lung cancer patients, but only partially decreased in other tumor patients. In vitro tissue culture test also showed that the transient increase of let-7 in human lung cancer cells could inhibit the proliferation of cancer cells, which also indicated that let-7 might be a tumor suppressor gene in lung tissue ( Takamizawa et al, 2004 ; Huang et al, 2020 ). It is also interesting to note that overall miRNA expression is lower in cancer cells than in normal cells.…”

Expression, Regulation and Functions of MicroRNAs in Autoimmune Hepatitis

“…It has been shown that let-7b (let-7b-5p) may play an important role in many biological processes and diseases including immune responses, neural cell differentiation and cancer [144][145][146]. Let-7b was found out to be down-regulated in the tumor tissues from different cancer patients [147][148][149]. Let-7b could target β-catenin and c-Myc and thus inhibit Wnt/β-catenin signaling pathway and suppress HCC cell proliferation [149].…”

“…Let-7b could target β-catenin and c-Myc and thus inhibit Wnt/β-catenin signaling pathway and suppress HCC cell proliferation [149]. Let-7b could target neuroblastoma RAS viral oncogene homolog (NRAS) and thus inhibit the Ras/Rho signaling pathway, leading to the suppression of prostate cancer cell proliferation, invasion and tumor growth and induction of cancer cell apoptosis [147]. Let-7b could target CEP126 (KIAA1377) and thus inhibit cancer cell proliferation, migration and invasion [150].…”