Silencing the expression of lncRNA SNHG15 may be a novel therapeutic approach in human breast cancer through regulating miR-345-5p

Minshu Zhu; Haifei Xiang; Zheng Peng; Zhaosheng Ma; Jianfei Shen; Tingting Wang; Lingyang Chen; Donghang Cao; Shanye Gu; Mingcang Wang; Jianbin Cao

doi:10.21037/atm-22-5275

Silencing the expression of lncRNA SNHG15 may be a novel therapeutic approach in human breast cancer through regulating miR-345-5p

Ann Transl Med. 2022 Nov;10(21):1173. doi: 10.21037/atm-22-5275.

Authors

Minshu Zhu^#^{1

2

3}, Haifei Xiang^#^{1

2

3}, Zheng Peng^{1

2}, Zhaosheng Ma³, Jianfei Shen², Tingting Wang^{1

2}, Lingyang Chen^{1

2}, Donghang Cao^{1

2}, Shanye Gu^{1

2}, Mingcang Wang^{1

2

3}, Jianbin Cao^{1

2

3}

Affiliations

¹ Department of Anesthesiology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China.
² Department of Surgical Oncology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China.
³ Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Linhai, China.

^# Contributed equally.

Abstract

Background: Long noncoding RNA (lncRNA) short nucleolar RNA host gene 15 (SNHG15) has been found to have an oncogenic function in numerous malignancies. Nevertheless, the biological function and regulatory mechanisms of SNHG15 in breast cancer have not been fully elucidated.

Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of SNHG15 and in MDA-MB-231 breast cancer cells. The expression of SNHG15 was silenced using small interfering RNA (siRNA) technology. The proliferation and migration of the cells were examined by colony formation assays, cell counting kit 8 (CCK-8) assays, and transwell assays. For the zebrafish xenograft injection experiments, cultured cells labelled with the fluorescent dye CM-DiI were injected into the perivitelline space of the larvae.

Results: This present study revealed that the expression of lncRNA SNHG15 (lnc-SNHG15) was significantly upregulated in breast cancer cells, and its overexpression was associated with the tumor. The relative expression of lnc-SNHG15 could be downregulated using siRNAs, and silencing lnc-SNHG15 inhibited the proliferation and the migration of MDA-MB-231 cells. In vivo experiments using the zebrafish xenograft model showed similar results. Mechanistically, the knockdown effect of lnc-SNHG15 could be restored by inhibiting the expression of the miR-345-5p, confirming the negative regulation between lnc-SNHG15 and miR-345-5p. Interestingly, cisplatin treatment combined with SNHG15 knockdown effectively inhibited MDA-MB-231 cell proliferation and migration in the zebrafish xenograft compared to negative controls.

Conclusions: In conclusion, lnc-SNHG15 knockdown increased miR-345-5p expression and negated cisplatin resistance in breast cancer cells, and thus, lnc-SNHG15 may be a potential novel target for breast cancer therapy.

Keywords: Cisplatin; SNHG15; human breast cancer; long noncoding RNA (lncRNA); miR-345-5p.