Molecular and cellular evidence for hsa‐miR‐1254 suppressor effect against HER2 signaling in breast cancer

Abstract

HER2 signaling upregulation is a hallmark of breast cancer which is the second cause of cancer‐related death in women. Here, we were looking for the candidate microRNAs which is capable of regulating the HER2 receptor and the genes of its downstream. To this aim, preliminary bioinformatics analysis introduced hsa‐miR‐1254 (miR‐1254) as a potential common regulator of HER2, HER3, PIK3R2, and AKT1 genes. Then, reverse‐transcription quantitative polymerase chain reaction (RT‐qPCR) analysis indicated a lower expression level of miR‐1254 in breast cancer specimens, compared to their normal pairs. Furthermore, overexpression of miR‐1254 resulted in HER2, HER3, PIK3R2, and AKT1 genes downregulation, detected by RT‐qPCR and confirmed by western blot analysis and enzyme‐linked immunosorbent assay test against AKT1, BAX, FADD, and HER2 protein levels in SKBR3 cells. Dual‐luciferase assay also supported direct interaction of miR‐1254 with MREs within 3' untranslated region sequences of HER2, HER3, PIK3R2, and AKT1 target genes. Overexpression of miR‐1254 in SKBR3 cells was followed by increased BAX/BCL2 expression ratio, detected by RT‐qPCR, and increased proportion of G1 cell population, detected by flow cytometry. Corroborated by cell cycle analysis, MTT, Annexin V‐FITC, and Live‐Dead cell staining assays, overexpression of miR‐1254 in MDA‐MB‐231 cells showed opposing results following the overexpression of miR‐1254. Taken together, results indicated that miR‐1254 acts as cell‐type‐specific tumor suppressor that targets HER2, HER3, PIK3R2, and AKT1 transcripts. These results suggest miR‐1254 as a potential therapeutic candidate for breast cancer subtypes.

In‐silico and in‐vitro evidence suggest LINC01405 as a sponge for miR‐29b and miR‐497‐5p, and a potential regulator of Wnt, PI3K, and TGFB signaling pathways in breast carcinoma

“…Here, we suggested that LINC01405 sponges miR‐29b and miR‐497 through which, it upregulated common target genes of these miRNAs, resulting in the upregulating of Wnt, PI3K, and TGFB signaling. Here, we took the first step to investigate the effect of LINC01405 on breast cancer, but it is necessary to conduct comprehensive study programs to find its role in different cancers and more breast cancer samples 35–38 …”

“…Here, we took the first step to investigate the effect of LINC01405 on breast cancer, but it is necessary to conduct comprehensive study programs to find its role in different cancers and more breast cancer samples. 35 , 36 , 37 , 38 …”

“…Here, we took the first step to investigate the effect of LINC01405 on breast cancer, but it is necessary to conduct comprehensive study programs to find its role in different cancers and more breast cancer samples. [35][36][37][38] Details associated with the LINC01405 (Loc100131138) function in the cell are represented by a schematic (Figure 8).…”

Plasma miR‐1254 as a predictive biomarker of chemosensitivity and a target of nucleic acid therapy in esophageal cancer

“…Previous reports show that miR‐1254 is downregulated in the serum of non‐small‐cell lung carcinoma (NSCLC) patients. 41 Additionally, numerous studies have demonstrated the various molecular functions of miR‐1254 as a pivotal tumor suppressor by targeting PSMD10 in colon cancer, 42 TFAP2A in NSCLC, 43 SMURF1 in gastric cancer, 44 CD36 in oral squamous cell carcinoma, 45 , 46 CSF1 in glioma, 47 NESG1 in nasopharyngeal carcinoma, 48 and ERBB2 in breast cancer, 49 although a few reports have shown the opposite effect. 50 , 51 However, the function of miR‐1254 in ESCC has remained unclear.…”

MicroRNA-135b-5p regulates trophoblast cell function by targeting phosphoinositide-3-kinase regulatory subunit 2 in preeclampsia

“…In the present study, PIK3R2 knockdown, similar to miR-135b-5p overexpression, blocked H/R-induced reduction in proliferation and angiogenesis, and promoted trophoblast cell apoptosis. Previous studies have reported that many miRNAs, such as miR-30a-5p, miR-126-3p and miR-1254-5p, can target PIK3R2 and regulate the progression of PE, non-small cell lung cancer, and breast cancer [ 20 , 60 , 61 ]. However, whether miR-135b-5p affects PE progression through PIK3R2 regulation was previously unclear.…”