Knockdown of long non-coding RNA HOST2 inhibits the�proliferation of triple negative breast cancer via regulation of the let-7b/CDK6 axis

Abstract

The upregulation of long non-coding RNA (lncRNA) human ovarian cancer-specific transcript 2 (HOST2) has been identified in breast cancer. The present study aimed to investigate whether lncRNA HOST2 regulated the proliferation of triple negative breast cancer (TNBC) cells, and the underlying molecular mechanism. In total, 30 patients with primary TNBC, who were treated at Wuhai People's Hospital (Wuhai, China), were recruited for the present study. Reverse transcription-quantitative polymerase chain reaction analysis was used for the examination of gene expression levels. A Cell Counting kit-8 (CCK-8) assay was used for the detection of cell proliferation. Phases of the cell cycle were evaluated by flow cytometry. Western blot analysis was performed to detect protein expression levels. A dual luciferase activity assay was performed to examine the interaction between microRNA (miRNA) and the 3' untranslated region (UTR) of target mRNA. The results revealed increased expression levels of HOST2 in tumor tissues from patients with TNBC. A positive correlation was identified between the expression of HOST2 and cyclin-dependent kinase 6 (CDK6) in tumor tissues. The silencing of HOST2 induced cell proliferation inhibition and cell cycle redistribution in MDA-MB-231 and MDA-MB-468 TNBC cells. In these two cell lines, HOST2 silencing caused a decrease in the phosphorylation of RB1 and CDK6, which was observed at the mRNA and protein levels. However, the silencing of CDK6 did not alter the expression of HOST2. It was hypothesized and confirmed that let-7b, a previously reported target miRNA of HOST2, was able to directly bind to the 3'UTR of CDK6 and repress its expression. The expression of let-7b was negatively correlated with the expression of HOST2 and CDK6 in tumor tissues. Overall, the data suggested that lncRNA HOST2 acts as an oncogene in TNBC via the upregulation of CDK6.

Inhibition of microRNA let‐7b expression by KDM2B promotes cancer progression by targeting EZH2 in ovarian cancer

“…Let‐7b suppresses tumor progression by targeting essential oncogenes. In breast cancer, 14 endometrial carcinoma, 15 and gastric cancer 16 let‐7b represses tumor malignancy by targeting CDK6, HMGA2, and ING1, respectively. In ovarian cancer, more investigations are necessary to characterize the direct targets of let‐7b.…”

“…The mechanisms regulating let‐7b expression in ovarian cancer are also not well understood. Several studies have shown that long non‐coding RNA (lncRNA) HOST2 (human ovarian cancer‐specific transcript 2) sequesters let‐7b in ovarian cancer, 10 cervical cancer, 19 gliomas, 20 and breast cancer 14 . Another study demonstrated that the genomic loss of let‐7b locus is one of the reasons for the low expression of let‐7b in ovarian cancer 21 .…”

Identification of miRNA-Based Signature as a Novel Potential Prognostic Biomarker in Patients with Breast Cancer

“…Besides, we also tested the expressions of these miRNAs (both OS-and RFS-related miRNAs) by comparing the high-risk and low-risk groups ( Figure S3) and found that the tendency of their expression was consistent with the univariate Cox regression test. In the MDA-MB-231 and MDA-MB-468 cells, Zhang et al [25] confirmed that the silencing of HOST2 induced cell proliferation inhibition and cell redistribution by the target miRNA of let-7b. Similarly, the let-7b miRNA gene was involved in the epithelial-to-mesenchymal transition process and cell growth in BC cells concerning Al-Harbi et al's report [26].…”

Sinomenine hydrochloride exerts antitumor outcome in ovarian cancer cells by inhibition of long non-coding RNA HOST2 expression

“…HOST2 is a newly discovered lncRNA, and it was originally found in ovarian cancer [16] and exerted proliferative effects and migration facilitation in ovarian cancer [17]. However, accumulating evidence proposes that HOST2 also plays a part in other cancer cells, such as hepatocellular carcinoma [28], breast cancer [29,30], pancreatic cancer [31], HPV-positive cervical cancer [32] and gastric cancer [33]. Therefore, the functions of HOST2 in cancer cells deserve further research.…”