Knockdown of collagen α‑1(III) inhibits glioma cell proliferation and migration and is regulated by miR128‑3p

Abstract

As a member of the collagen family, collagen α-1(III) (COL3A1) is an important protein in the development and progression of several tumors. However, the role of COL3A1 in glioma is not yet clear. The present study examined the expression and function of COL3A1 in glioma cell behavior and identified microRNA (miRNA) regulators. It was demonstrated that COL3A1 expression was upregulated in glioma and directly correlated with the tumor grade. Analysis of the GSE4290 and GSE7696 profiles acquired from the Gene Expression Omnibus database also revealed an increased COL3A1 expression in malignant gliomas compared with the lower grade gliomas and non-tumor brain tissue, which was directly correlated with glioma grade. To explore the functional role of COL3A1 in glioma cell growth, small interfering RNA interference was applied to inhibit COL3A1 expression in Hs683 and U251 cells. The relative COL3A1 mRNA and protein expression levels were significantly reduced in the knockdown cells as determined by western blot analysis. In addition, decreased COL3A1 expression in Hs683 and U251 glioma cells resulted in a delay in cell growth and colony disruption as determined by MTS and colony formation assays. Wound healing analysis indicated that cells with suppressed expression of COL3A1 had a reduced ability to migrate. COL3A1 mRNA levels were inversely correlated with the miR128-3p level in glioma, suggesting that miR128-3p expression is associated with COL3A1 inhibition as verified by reverse transcription-quantified polymerase chain reaction. These results suggest that COL3A1 may be a novel regulator of glioblastoma cell behavior and may represent a novel target for gene therapies against glioma.

Type III collagen (COL3A1): Gene and protein structure, tissue distribution, and associated diseases

“…Type III collagen expression has also been evaluated in cancer. In one study where 33 glioma tissues samples were analyzed, a significant increase in COL3A1 mRNA levels was found and the increased expression correlated with the tumor grade with high grade gliomas showing the highest levels of expression (Gao et al, 2018). Immunohistological staining of glioma tissues demonstrated the same results on the protein level.…”

Use of Genome-Scale Integrated Analysis to Identify Key Genes and Potential Molecular Mechanisms in Recurrence of Lower-Grade Brain Glioma

“…The second hub gene, COL3A1, encodes collagen alpha-1 (III) chain, a protein which is a precursor to collagen III, continually combined with type I collagen. As a member of the collagen family, collagen alpha-1 (III) (COL3A1) is an important protein in the development and progression of several tumors, as it induces profound angiogenic responses in the host brain microvasculature that promote tumor growth [36,37]. Moreover, some studies determined that COL3A1 expression was upregulated in glioma and was directly correlated with the tumor grade [36,38].…”

“…As a member of the collagen family, collagen alpha-1 (III) (COL3A1) is an important protein in the development and progression of several tumors, as it induces profound angiogenic responses in the host brain microvasculature that promote tumor growth [36,37]. Moreover, some studies determined that COL3A1 expression was upregulated in glioma and was directly correlated with the tumor grade [36,38]. As COL3A1 localizes to the extracellular matrix and was selectively expressed by the microvasculature, it may be a novel regulator of glioblastoma cell behavior and may be a suitable biomarker for diagnostic use or as a novel target for gene therapies against glioma [37,38].…”

Lnc-GULP1-2:1 Affects Granulosa Cell Proliferation by Regulating COL3A1 Expression and Localization​

“…Studies have shown that several miRNAs can play a role in different diseases by down-regulating the expression of COL3A1 and inhibiting the proliferation of corresponding cells [30][31][32][33], indicating that the abnormal expression of COL3A1 plays an important role in the proliferation and development of various cells. There are also studies found that the expression of COL3A1 in cumulus cells is elevated under the stimulation of FSH [34], and FSH has the function of promoting granulosa cell proliferation [35,36], indicating that COL3A1 may affect the proliferation of granulosa cells. Our study showed that COL3A1 expression levels were signi cantly different in granulosa cells from patients with different ovarian reserve, and downregulation of COL3A1 signi cantly inhibited granulosa cell proliferation, suggesting that COL3A1 expression is associated with ovarian function, at least in part, by regulating granulosa cell proliferation.…”