MicroRNA‑26a inhibits cell proliferation and invasion by targeting FAM98A in breast cancer

Abstract

MicroRNAs (miRNAs/miRs) play key roles in cancer progression. Extensive research has revealed that miR-26a is abnormally expressed and functions as a tumor suppressor in numerous types of cancer. Thus, the present study was undertaken to investigate the regulatory role and potential mechanism of action of miR-26a in breast cancer. Furthermore, the present study aimed to examine the alterations in miR-26a expression and its effects on human breast cancer cells. Reverse transcription-quantitative PCR was conducted to assess the differences in miR-26a expression between human breast cancer and normal breast specimens. A Cell Counting Kit-8 assay and cloning experiments were used to detect cell proliferation and clone formation. Wound healing and Transwell assays were performed to examine cell migration and invasion. A luciferase activity experiment was utilized to validate the association between miR-26a and family with sequence similarity 98 member A (FAM98A). Western blotting was conducted to detect the protein expression levels of FAM98A, sonic hedgehog signaling molecule (SHH), smoothened, frizzled class receptor (SMO) and GLI family zinc finger 1 (GLI1). The results indicated that miR-26a expression was decreased in breast carcinoma tissues and cell lines. Moreover, overexpression of miR-26a significantly suppressed cell proliferation, clone formation ability and metastasis, and it sensitized breast cancer cells to docetaxel. It was demonstrated that miR-26a directly targeted FAM98A, and that FAM98A, SHH, SMO and GLI1 expression levels were decreased in cells transfected with miR-26a mimics. Collectively, the results of the present study suggested that miR-26a negatively regulated the expression of FAM98A, indicating that it may play a key role in the suppression of breast carcinogenesis.

Identification of key serum biomarkers for the diagnosis and metastatic prediction of osteosarcoma by analysis of immune cell infiltration

“…In this study, FAM98A was considered to be a novel biomarker for OS metastasis. Previously, FAM98A was shown to promote progression of endometrial carcinoma, non-small cell lung cancer, and breast cancer [ 64 – 66 ]. Moreover, FAM98A was related to poor prognosis and metastasis [ 64 ].…”

Identification of the Key Serum Biomarkers to Diagnose and Predict Metastasis of Osteosarcoma Based on the Analysis of Immune Cell Infiltration Characteristics

“…FAM98A, the novel important factors and promising markers, was veri ed in serum sample and highlighted about metastasis rstly in OS. Literatures were reported that FAM98A promotes cancer progression in endometrial carcinoma, non-small cell lung cancer, and breast cancer and show correlation of poor prognosis and metastasis [60][61][62] . And the most noteworthy is that FAM98A participates in the regulation of bone homeostasis and its inhibition leads to bone resorption defects.…”

Emerging role of non-coding RNAs in the regulation of Sonic Hedgehog signaling pathway

“…Up-regulation of this miRNA has resulted in down-regulation of FAM98A, SHH, SMO and GLI1. Taken together, miR-26a suppresses breast carcinogenesis through inhibiting expression of FAM98A, and decreasing activity of Shh pathway [ 20 ]. miR-1471 is another down-regulated miRNA in breast cancer cells.…”

“…Further experiment has validated that lncRNA LOC101930370 can significantly elevate SHH and Gli-1 expression via sponging miR-1471, therefore promoting cell proliferation and metastasis in breast cancer cells by modulating the hedgehog cascade [ 21 ]. Moreover, another research has pointed out that miR-26a has a remarkable part in suppressing breast cancer cell proliferation and invasion via downregulating the expression levels of FAM98A, SHH, SMO and GlI1, thereby inactivating the sonic hedgehog pathway in tumor cells [ 20 ] …”

“…Expression assays in clinical samples from a variety of tumor types have indicated down-regulation of Shh-targeting miRNAs such as miR-26a [ 20 ] and miR-1471 [ 21 ] in breast cancer, miR-129-5p in cervical cancer [ 28 ], miR-361-3p in retinoblastoma, miR-26b-5p in gallbladder carcinoma [ 33 ], and miR-361-3p in retinoblastoma [ 53 ]. In gallbladder cancer, dysregulation of miR-26b-5p has been associated with age and sex of patients, tumor invasion, differentiation degree, tumor location, and TNM stage [ 33 ].…”