RSRC1 suppresses gastric cancer cell proliferation and migration by regulating PTEN expression

Abstract

Arginine/serine-rich coiled coil 1 (RSRC1) is a gene which plays a significant role in the constitutive and alternative splicing of mRNA and transcriptional regulation. It has been implicated in various neurological disorders, as well as in cancer. However, its role in gastric cancer (GC) remains unknown. Thus, the present study aimed to investigate the role of RSRC1 in GC. RSRC1 expression in GC tissues was determined by RT-qPCR and immunohistochemical staining. The effects of RSRC1 on cell proliferation and migration were detected using a Cell Counting Kit-8 assay, 5-ethynyl-2′-deoxyuridine (EdU) incorporation assay and a Transwell migration assay. Western blot analysis and RT-qPCR were used to explore the molecular mechanisms of of action of RSRC1 in GC. The results indicated that RSRC1 expression was downregulated in GC tissues compared to paired normal tissues and the reduced expression of RSRC1 was shown to contribute to a poor prognosis of patients with GC. RSRC1 knockdown promoted the proliferation and migration of GC cells. In addition, the knockdown of RSRC1 decreased the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a potent tumor suppressor gene controlling cellular growth and viability. On the whole, the findings of the present study indicate that RSRC1 functions as a tumor suppressor gene in GC and that it may exert its effects by regulating PTEN expression.

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“…PUSL1 encodes an inner membrane–associated mitochondrial matrix protein required for efficient mitochondrial translation ( 28 ). RSRC1 encodes a member of the serine- and arginine-rich–related protein family, associated with altered brain function in schizophrenia, and may also be associated with cancer cell proliferation and migration ( 29 , 30 ). Genome-wide association studies have shown that single-nucleotide polymorphisms of RSRC1 are associated with schizophrenia ( 31 , 32 ), and its mutation causes intellectual disability, aberrant behavior, hypotonia, and mild facial dysmorphism ( 30 ).…”

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“…Total proteins were extracted from cultured GC cells with RIPA buffer, and the supernatants were diluted in 5×SDS loading buffer after calculating protein concentration with a Pierce BCA protein assay kit (Takara, Japan). Western blot assay was carried out in accordance with the previous report (Yu et al 2019 ). The signal bands were detected by Odyssey Infrared Imaging System (Li-COR Biosciences) based on manufacturer's instructions.…”

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“…The corresponding protein localises to lipid droplets and increased levels of lipid droplets have been found in EA versus BE and BE versus normal tissue 50 . RSRC1 at 3p25 is involved in mRNA splicing and may suppress gastric cancer cell proliferation 51 . BTN3A2 at 4q34 is a coregulator of T-cells and NK-cells in immune responses 52.…”