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Knockdown of ribosomal protein S15A inhibits proliferation of breast cancer cells through induction of apoptosis in vitro.

ABSTRACT: To explore the role of ribosomal protein S15A (RPS15A) in breast cancer. The Oncomine database was used to compare the expression of RPS15A in human breast cancer tissues and normal tissues. RPS15A in breast cancer cell line ZR-75-30 and BT474 was specifically knocked down using lentivirus-mediated short hairpin RNAs (shRNAs). RPS15A knockdown efficiency was validated by quantitative polymerase chain reaction and western blot analysis. Subsequently, the functional effects of RPS15A on proliferation of breast cancer cells were investigated by MTT, colony formation and flow cytometry assays. Functional analysis indicated that RPS15A knockdown could inhibit cell proliferation, induced cell cycle arrest and apoptosis. Mechanism analysis revealed RPS15A mediated apoptosis via activating of caspase-3 and PARP cleavage, upregulating of Bad and BAX and downregulating of Bcl-2. Our preliminary study highlighted the importance of RPS15A in breast cancer growth. The inhibition of RPS15A may be a promising therapeutic target for breast cancer treatment.

SUBMITTER: Feng W

PROVIDER: S-EPMC6214850 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Knockdown of ribosomal protein S15A inhibits proliferation of breast cancer cells through induction of apoptosis in vitro.

Feng Weiliang W Liang Chenlu C Wang Chen C Yu Xingfei X Li Qinglin Q Yang Hongjian H

Cytotechnology 20180525 5

To explore the role of ribosomal protein S15A (RPS15A) in breast cancer. The Oncomine database was used to compare the expression of RPS15A in human breast cancer tissues and normal tissues. RPS15A in breast cancer cell line ZR-75-30 and BT474 was specifically knocked down using lentivirus-mediated short hairpin RNAs (shRNAs). RPS15A knockdown efficiency was validated by quantitative polymerase chain reaction and western blot analysis. Subsequently, the functional effects of RPS15A on proliferat ...[more]

PMID: 29802490

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Project description:The transcription factor STAT6 is strongly expressed in various tumours and is most highly expressed in human malignant lymphomas and pancreatic, colorectal, prostate and breast cancers. STAT6 is associated with cancer cell proliferation, an increased malignancy and poor prognosis. Thus, techniques aimed at reducing or blocking STAT6 expression may be useful in treating STAT6high cancers. Among these cancers, colorectal and breast cancers represent two of the most common worldwide and their incidence is increasing every year. In 2018, colorectal and breast cancers represented 10.2% and 11.6% of all new cases of cancer diagnosed, respectively. In this study, four proprietary STAT6 specific small interfering RNA (siRNA) sequences were tested in vitro using the human colon adenocarcinoma cell line, HT-29, and the breast/duct carcinoma cell line, ZR-75-1. Decreases in STAT6 mRNA and protein levels were analysed to confirm the transfection was successful and STAT6 knockdown effects were measured by analysing cell proliferation and apoptosis. Results showed that 100nM siRNA concentration was the most effective and, although all individual sequences were capable of significantly inhibiting cell proliferation, STAT6 siRNA sequences 1 and 4 had the largest effects. STAT6 silencing also significantly induced apoptotic events. In conclusion, these results demonstrate that STAT6 siRNA sequences are capable of inhibiting proliferation of and inducing apoptosis of HT-29 colorectal cancer cells and ZR-75-1 breast cancer cells, halving the number of cancer cells in a short period of time. These experiments will be repeated in other STAT6high cancers in vitro, and animal studies in immunocompromised mice have been planned using xenografts of STAT6-expressing human colorectal and breast cancer cells. The STAT6 siRNA sequences therefore represent a potential treatment for STAT6high colorectal and breast cancers and a wide variety of other STAT6-expressing cancers.

Dataset Information

Knockdown of ribosomal protein S15A inhibits proliferation of breast cancer cells through induction of apoptosis in vitro.

Publications

Knockdown of ribosomal protein S15A inhibits proliferation of breast cancer cells through induction of apoptosis in vitro.

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