Long non-coding RNAs (lncRNAs) have involved in human malignancies and played an important role in gene regulations. The dysregulation of lncRNA
MIR22HG
has been reported in several cancers. However, the role of
MIR22HG
in esophageal adenocarcinoma (EAC) is poorly understood. Loss of function approaches were used to investigate the biological role of
MIR22HG
in EAC cells. The effects of
MIR22HG
on cell proliferation were evaluated by WST-1 and colony formation assays. The effects of
MIR22HG
on cell migration and invasion were examined using transwell assays. QRT-PCR and Western blot were used to evaluate the mRNA and protein expression of related genes. In this study, abrogation of
MIR22HG
inhibited cell proliferation, colony formation, invasion and migration in EAC 3 cell lines (OE33, OE19 and FLO-1). Mechanistically,
MIR22HG
silencing decreased the expression of STAT3/c-Myc/p-FAK proteins and induced apoptosis in EAC cell lines. These results delineate a novel mechanism of
MIR22HG
in EAC, and may provide potential targets by developing lncRNA-based therapies for EAC.
Long non-coding RNAs play critical roles in the development of lung cancer by functioning as tumor suppressors or oncogenes. Changes in the expression of LINC01279 have been associated with cell differentiation and human diseases. However, the mechanism underlying LINC01279 activity in tumorigenesis is not clear. Here, we analyzed the function of LINC01279 in lung adenocarcinoma using clinical samples, xenografts, and non-small-cell lung cancer cell lines. We found that LINC01279 is highly expressed in lung adenocarcinoma and may be considered as a predictive factor for this cancer. Knockdown of LINC01279 prevents tumor growth in xenografts and in cancer cell lines by activating autophagy and apoptosis. Molecularly, we revealed that LINC01279 regulates the expression of focal adhesion kinase and extracellular-regulated kinase signaling. In addition, it complexes with and stabilizes the transcriptional co-repressor SIN3A protein. Suppression of focal adhesion kinase and SIN3A also induces apoptosis and prevents tumor progression, suggesting that they may at least in part mediate the oncogenic activity of LINC01279. These results identify LINC01279 as a possible oncogene that plays an important role in the development of lung cancer. Our findings provide insights into the mechanism underlying LINC01279-mediated oncogenesis of lung adenocarcinoma. They may help to discover potential therapeutic targets for cancer diagnosis and prognosis.
Background: In human lung adenocarcinoma (LUAD) tissues, Long noncoding RNA LINC01279 is significantly upregulated. However, the functions of LINC01279 in LUAD is yet to be clarified.Methods: In situ hybridization was employed to investigate the difference between expression of LINC01279 in LUAD and in normal tissues. The result of in situ hybridization is verified by qRT-PCR. Cytoplasmic and nuclear experiments showed that LINC01279 was mainly located in the cytoplasm of lung cancer cells. The loss of function experiment showed that LINC01279 could inhibit the proliferation, colony formation, invasion and migration of lung cancer cells. The interaction between SIN3A and LINC01279 was confirmed by RIP test. At the same time, through western bolt, we found that LINC01279 plays a key role in the regulation of apoptosis and autophagy in lung adenocarcinoma.Results: Our study confirmed that LINC01279 was upregulated in LUAD tissues, the knocking-down of which significantly inhibited the growth of LUAD cancer cells both in vitro and in vivo. Mechanistic investigations revealed that LINC01279 could directly interact with SIN3A and modulate the FAK and ERK protein expression in the cytoplasm. Moreover, the proteins of PARP and LC3B, P62, Beclin-1, respectively related with apoptosis and autophagy, were changed after LINC01279 siRNA. Conclusions: Taken together, our research found that LINC01279 which is significantly up-regulated in LUAD tissues and cell lines, and promotes the changes of FAK and ERK proteins in downstream pathways by combining with SIN3A, promotes the proliferation of LUAD cells, and inhibits apoptosis and autophagy. The results of this work illustrated how LINC01279 is part of a regulatory network that contributes to the oncogenesis of LUAD and proposed LINC01279 could be a potential target for LUAD diagnosis and treatment.
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