miR-877-5p antagonizes the promoting effect of SP on the gastric cancer progression

Abstract

Gastric cancer is one of the four major tumors in the world and the second leading cause of cancer-related death. It was reported that Substance P (SP), as an oncogenic factor, could regulate the expression of miRNAs in gastric cancer progression. Here, we focused on the role of miR-877-5p in gastric cancer development and the miR-877-5p involvement in the SP-mediated gastric cancer development. The mRNA expression level and cell proliferation were assessed by quantitative real-time PCR and cell counting kit-8 assay, respectively. Flow cytometry was conducted to detect apoptosis, followed by assessing the expression of related apoptosis factors. Dual-luciferase reporter assay was performed to validate the interaction between miR-877-5p and Forkhead cassette M1 (FOXM1). Our results showed that SP treatment significantly increased cell proliferation in gastric cancer. Moreover, the miR-877-5p expression was dose-dependently decreased by SP, whereas FOXM1 expression was markedly increased by SP in gastric cancer cells. miR-877-5p negatively regulated gastric cancer development via inhibiting cell p roliferation and promoting apoptosis accompanied by increased cleaved caspase-3, cleaved caspase-9, and bax protein levels and decreased bcl-2 level. We confirmed that miR-877-5p could target FOXM1 and negatively regulate its expression. Furthermore, we demonstrated that SP could promote cell proliferation and inhibit apoptosis, while miR-877-5p overexpression reversed the effect of SP on cell proliferation and apoptosis. These results suggest that miR-877-5p overexpression can antagonize the promoting effect of SP on the development of gastric cancer, indicating that miR-877-5p may serve as a promising therapeutic target for gastric cancer.

A Comprehensive Study on Signal Transduction and Therapeutic Role of miR-877 in Human Cancers

“…At the functional level, some studies have shown that miR-877 promotes cell proliferation and invasion and induces cell apoptosis in many cancers. [ 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 ] The study collected prove to support the molecular mechanism and clinical conspicuousness of miR-877 in several cancers.…”

“…FOXM1 is known to play a key role in cell cycle progression where endogenous FOXM1 expression peaks at S and G2/M phases. Guo et al .,[ 23 ] (2020) verified miR-877-5p capability of targeting FOXM1 and negative regulation of its expression. Another study showed the ability of miR-877-5p for negative regulation of the GC progression through suppressing the rapid growth or proliferation of the cells and elevating apoptosis that may be followed by greater cleaved caspase-3 and caspase-9, as well as level of Bax protein and lower levels of Bcl-2.…”

“…Several studies has shown that miR-877 has been dysregulated in a variety of human tumors such as bladder cancer,[ 12 ] cervical cancer,[ 13 14 15 ] cholangiocarcinoma,[ 16 ] colorectal cancer (CRC),[ 17 18 19 ] gastric cancer,[ 20 21 22 23 24 ] glioblastoma,[ 25 26 27 ] head and neck squamous cell carcinoma (HNSCC),[ 28 ] hepatocellular carcinoma,[ 29 30 31 32 33 34 ] laryngeal squamous cell carcinoma,[ 35 ] melanoma,[ 36 ] non-small cell lung cancer (NSCLC),[ 37 38 39 40 ] ovarian cancer (OC),[ 41 ] pancreatic ductal Adenocarcinoma,[ 42 43 ] as well as renal cell carcinoma (RCC)[ 44 ] [ Table 1 ].…”

Identification of Novel Immune-infiltration Related miRNAs that can Predict the Prognosis of Patients with Hepatocellular Carcinoma

“…We further examined the main hub Treg-related miRNAs (hsa-miR-877 and hsa-miR-137), which we showed were independent indicators of poor outcome. Hsa-miR-877 was found to be overexpressed in gastric cancer, and also antagonized the promoting effect of Substance P in the occurrence and progression of gastric cancer, suggesting that miR-877-5p could be a potential drug target [47] . Further, miR-877-5 has been reported to participate in gene regulation of competing endogenous RNA (ceRNA) mechanisms in multiple tumors, including cervical cancer, malignant gliomas, and non-small-cell lung cancer [48][49][50] .…”

CircPIK3C2A Facilitates the Progression of Glioblastoma via Targeting miR-877-5p/FOXM1 Axis

“…Numerous studies have demonstrated the dysregulation of miRNA expression in human cancers through various mechanisms (10,11). miR-877-5p has been proved to a tumor suppressor that is involved in the development of several types of cancer, including hepatocellular carcinoma (HCC) (12), non-small cell lung cancer (NSCLC) (13), gastric cancer (14) and cervical cancer (15). miR-877-5p also functions to constrain the proliferative capacity of GBM cells (16).…”