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miR-135a acts as a tumor suppressor in gastric cancer in part by targeting KIFC1
Chuanlei Zhang1, Xiaoqi Chen1, Xinju Chen1
1Department of Digestive Diseases, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, People's Republic of China.
Abstract:
miR-135a was downregulated in the majority of human primary gastric cancer (GC) tissues and GC cell lines. Kinesin family member C1 (KIFC1) was significantly upregulated in GC tissues and cell lines and promoted GC development and progression. We searched for miR-135a targets by using MiRanda, TargetScan, and PicTar tools, and found that KIFC1 was a potential target of miR-135a. Based on these findings, we speculated that miR-135a might target KIFC1 to inhibit GC growth. We determined the expression of miR-135a and KIFC1 by quantitative real-time polymerase chain reaction and Western blot assays, respectively, and found downregulation of miR-135a and upregulation of KIFC1 in GC tissues and cell lines. Cell proliferation and apoptosis assays showed that knockdown of KIFC1 inhibited proliferation and promoted apoptosis of GC cells, and miR-135a mimics had similar effects on GC cell proliferation and apoptosis. Furthermore, we verified that KIFC1 was a direct target of miR-135a, which confirmed our speculation that the functional effect of miR-135a on GC cells, at least, in part, depends on KIFC1. These findings suggest that miR-135a has an important role in the suppression of GC and presents a novel mechanism of miRNA-mediated KIFC1 expression in cancer cells.
Insights
MicroRNA-135a (miR-135a) suppresses gastric cancer (GC) by targeting Kinesin family member C1 (KIFC1). Downregulation of miR-135a and upregulation of KIFC1 are observed in GC, with miR-135a inhibiting tumor growth.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Gastric cancer (GC) is a major global health concern with complex molecular underpinnings.
- MicroRNAs (miRNAs) play critical roles in cancer development and progression.
- Dysregulation of specific miRNAs, like miR-135a, is implicated in various cancers.
Purpose of the Study:
- To investigate the role of miR-135a in gastric cancer.
- To identify the molecular targets of miR-135a in GC.
- To elucidate the mechanism by which miR-135a affects GC cell behavior.
Main Methods:
- Bioinformatic tools (MiRanda, TargetScan, PicTar) were used to predict miR-135a targets.
- Quantitative real-time PCR and Western blot assays were employed to measure gene and protein expression.
- Cell proliferation and apoptosis assays were conducted to assess functional effects.
Main Results:
- miR-135a was found to be downregulated in human primary GC tissues and cell lines.
- Kinesin family member C1 (KIFC1) was upregulated in GC and identified as a direct target of miR-135a.
- miR-135a mimics inhibited GC cell proliferation and promoted apoptosis, while KIFC1 knockdown yielded similar results.
Conclusions:
- miR-135a acts as a tumor suppressor in gastric cancer.
- The tumor-suppressive function of miR-135a is, at least partially, mediated through the inhibition of KIFC1.
- This study reveals a novel mechanism of miRNA-mediated KIFC1 regulation in cancer cells.
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