Abstract
Gastric cancer has higher morbidity and mortality than other cancers for the low diagnosis rate and few therapies. MiR-195 has been reported to be involved in the occurrence, development and prognosis of various cancers. However, the function of miR-195 in gastric cancer remains largely unknown. Herein, the aims of this study were to probe the functional mechanism of miR-195 and its chemotherapy sensitivity as well as clinical prognosis in gastric cancer. We screened out low-expressed miR-195 through microarray analysis and further confirmed miR-195 was widely down-regulated in gastric cancer cells. Subsequently, AKT3 was identified as the direct target gene of miR-195 by target gene prediction software, dual luciferase reporter assay and western blot. Functional assays indicated that miR-195 acted as a tumor suppressor through regulating the proliferative, migrated and invasive properties of gastric cancer cells in vitro, and intratumoral delivery of miR-195 significantly suppressed tumor growth in vivo. Additionally, we also found miR-195 overexpression could enhance the chemotherapy sensitivity of cisplatin in gastric cancer cells and prolong the overall survival and progression free survival of gastric cancer patients. Collectively, our findings demonstrate miR-195 may be of great significance on early diagnosis of gastric cancer, providing the theoretical basis for prognosis and recurrence risk.
Highlights
MicroRNAs are endogenous noncoding regulatory RNAs with 17-25 nucleotides, which play vital roles in post-transcriptional gene regulation [1]
Those differentially expressed miRNAs are frequently located at fragile sites which are generally implicated in cancer occurrence [5]
Plentiful studies have proved that that miRNAs exist in the variable genome involved in cancers, which makes researchers focus on the role of miRNAs in the process of cancer development [24]
Summary
MicroRNAs (miRNAs) are endogenous noncoding regulatory RNAs with 17-25 nucleotides, which play vital roles in post-transcriptional gene regulation [1]. More than 2,000 miRNAs have been registered in the “miRBase” database [2]. MiRNAs are strongly linked with biological processes consisting of cell proliferation, metastasis, differentiation, and apoptosis [3, 4]. Mounting evidence has demonstrated that multiple miRNAs are abnormally expressed in human cancers and functionally participate in regulation of various pathological processes www.impactjournals.com/oncotarget during tumor initiation and progression [5]. Several miRNAs have been identified as either oncogenes or tumor suppressors. MiR-195 as a tumor-suppressive miRNA is correlated with metastases and recurrences of gastric cancer (GC) [6], breast cancer [7], and human cervical cancer [8], while miR-21 as a well-characterized oncogenic miRNA is overexpressed in breast cancer, colorectal cancer, lung cancer, GC and so on [9,10,11,12]
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