<p>LncRNA-SNHG7 Enhances Chemotherapy Resistance and Cell Viability of Breast Cancer Cells by Regulating miR-186</p>

Abstract

Background: Clinical tolerance to trastuzumab greatly affects the therapeutic effect in breast cancer (BC). Long-chain non-coding RNA (lncRNA) plays an important role in the development of trastuzumab resistance, in which SNHG7 can promote the epithelial mesenchymal transformation (EMT) of breast cancer cells into, while EMT is related to trastuzumab resistance of breast cancer cells. Objective: To investigate whether lncRNA-SNHG7 can enhance chemotherapy resistance and cell viability of BC cells by regulating miR-186. Methods: SK-BR-3 and SNHG7 of HER2+BC cells were induced to enhance the resistance of BC cells to trastuzumab by regulating miR-186, and to regulate the expression levels of SNHG7 and miR-186. The sensitivity of drug-resistant cells to trastuzumab and the changes of cell proliferation, migration, apoptosis, and EMT were measured and verified by tumorigenesis in vivo. The effects of miR-186 on SNHG7 were investigated through rescue experiments; the regulatory relationship between the expression of SNHG7 and miR-186 was verified by the double luciferase reporter (DLR) and the mechanism of SNHG7 was explored. Results: Down-regulation of SNHG7 or up-regulation of miR-186 could increase the sensitivity of BC cells to trastuzumab, inhibit the proliferation, migration and EMT, and promote apoptosis. Compared with the down-regulation of SNHG7 or miR-186 alone, simultaneous down-regulation of SNHG7 and miR-186 on drug-resistant cells brought notably lower sensitivity to trastuzumab and apoptosis rate, and higher proliferation and apoptosis ability. The DLR showed that miR-186 could specifically inhibit the expression of SNHG7. The results of tumorigenesis in vivo revealed that down-regulation of SNHG7 or up-regulation of miR-186 could improve the therapeutic effect of trastuzumab and reduce the tumor volume, and miR-186 could also antagonize the effect of SNHG7. Conclusion: Down-regulation of SNHG7-targeted miR-186 can reverse trastuzumab resistance of BC cells, inhibit the proliferation, migration, and EMT levels of BC cells, and promote apoptosis.

Prognostic Effect of lncRNA SNHG7 On Cancer Outcome: A Meta and Bioinformatic Analysis

“…Furthermore, SNHG7 may act as a competitive endogenous RNA (ceRNA) to aggravate the development of cancers. Elevated lncRNA SNHG7 may reduce the miRNAs expression level, such as miR34a, miR3243p, miR503, miRNA381, miR186, miR216b and miR5095 in multiple cancers (25,26,(40)(41)(42)(43)(44).Taken together, these articles demonstrated that SNHG7 plays an important role in tumor development and progression. These evidences encouraged us to investigate the correlation between SNHG7 expression levels and cancer prognosis.…”

Serum exosomal lncRNA SNHG7 is increased in NSCLC and predicts unfavorable prognosis

“…High SNHG7 expression was closely associated with tumor stage, lymph node metastasis and worse overall survival of BC patients. SNHG7 inhibition enhanced the sensitivity of BC cells to trastuzumab, reduced cell proliferative, invasive abilities and promoted cell apoptosis by upregulating miR-186 [23,24]. In gastric cancer (GC), high expression of SNHG7 occurred more frequently in in cancerous tissues and cell lines.…”

Oncogenic Roles of Small Nucleolar RNA Host Gene 7 (SNHG7) Long Noncoding RNA in Human Cancers and Potentials

“…Conferring chemoresistance or desensitization has been concluded from cellular studies in which increased sensitivity of cancer cells to conventional chemotherapy agents and/or radiotherapy is seen on SNHG7 knockdown. For example, in two distinct experiments, enhanced sensitivity of breast cancer cells to Adriamycin and Trastuzumab is shown when SNHG7 is silenced or its target sponged miRNA (miR-34a or miR-186, respectively) is overexpressed ( Li et al, 2020a ; Zhang et al, 2020b ). Knockdown studies employing RNA silencing confirm the overexpression experiment results by reversing the SNHG7 impacts on malignant cells behaviors.…”