MicroRNA-885 regulates the growth and epithelial mesenchymal transition of human liver cancer cells by suppressing tropomodulin 1 expression
Introduction
The human liver cancer is one of the most prevalent and highly aggressive human cancers, worldwide [1]. At the global level, every year more than the half of the liver cancer cases and deaths are reported from China alone [2]. The reports suggest that this malignancy is least sensitive to chemo and radiotherapy. The only seemingly effective therapeutic method is the surgical resurrection or transplantation of the liver [3]. The poor diagnosis at early stages, metastasis to distant tissues and higher recurrence rates of liver cancer are other major cancer management hindrances [4]. Therefore, it is being urgently felt that alternative ways of management of liver cancer must be explored. In this regard, the non-coding RNAs including microRNAs (miRs) have been investigated for their cancer regulatory roles in the recent years. The miRs are a class of short endogenous RNAs which play role in gene slicing by binding to the untranslated regions (UTRs) of specific target mRNAs [5]. The miRs have been found to regulate the major pathways of cell differentiation, proliferation, and apoptosis [6]. They also play crucial role in cancer growth and progression together with regulating the cancer metastasis [7]. The microRNA-885 (miR-885) acts as tumor-suppressor and has been found to regulate the proliferation of several human cancers [8]. It also experiences considerable regulatory control in liver cancer mechanics [9]. However, the regulatory role of miR-885 has not been studied via regulation of tropomodulin 1 (TMOD1) expression in liver cancer. Thus, the present study focused on the exploration of miR-885/TMOD1 molecular axis in liver cancer. It was found that TMOD1 is targeted by miR-885 in liver cancer. Enhanced expression of TMOD1 due to the transcriptional repression of miR-885, greatly accounts for enhancement of liver cancer proliferation and cellular transition from epithelial to mesenchymal state. The study suggests miR-885 as tumor-suppressor and therapeutic molecular agent in liver cancer.
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Tissues and cell lines
The hepatocellular carcinoma tissues and adjacent paired normal tissues were obtained for the liver cancer patients admitted in Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China through proper consent. At total of 100 pairs of clinical tissues were used in the study under the ethical guidelines of the Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. The characteristics of the patients used in the study are listed in Table 1. The
Transcriptional repression of miR-885 in liver cancer
The real time expression study was undertaken to examine the transcript level of miR-885 in normal and cancerous liver tissues. The latter showed significant (P < 0.05) repression of miR-885 expression (Fig. 1A). The expression was also inferred from the normal (THLE-2) and cancerous (SNU-182, SNU-423, SNU-449, SNU-475 and HepG2) liver cell lines. miR-885 was found to exhibit significant (P < 0.05) level of transcriptional repression in all five cancer cell lines (Fig. 1B). Among the cancer
Discussion
The current study insights into the prognostic and therapeutic role of miR-885 in liver cancer. Confirming the previous findings, miR-885 was downregulated in liver cancer [10,11]. Overexpression of miR-885 resulted in significant decline in the proliferation of the liver cancer cells. Similar results have been observed previously in other cancer types, for instance, miR-885 has been reported to suppress the proliferation, migration, and invasion osteosarcoma cells [12]. Similarly, miR-885 has
Conclusions
Taken together, miR-885 acts a tumor suppressor in liver cancer and regulates the proliferation and epithelial to mesenchymal transition of liver cancer cells. The study revealed the therapeutic potential of miR-885/TMOD1 axis in the management of liver cancer.
Declaration of competing interest
Authors declare that there are no conflicts of interest.
References (24)
- et al.
Heterogeneity of liver cancer and personalized therapy
Canc. Lett.
(2016) - et al.
Cancer incidence and mortality in China, 2013
Canc. Lett.
(2017) - et al.
A global view of hepatocellular carcinoma: trends, risk, prevention, and management
Nat. Rev. Gastroenterol. Hepatol.
(2019) - et al.
MicroRNA and cancer–a brief overview
Ad. Biol. Reg.
(2015) - et al.
Cancer metastasis: building a framework
Cell
(2006) - et al.
Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis
Dev. Cell
(2008) - et al.
Epithelial–mesenchymal transition and the invasive potential of tumors
Trends Mol. Med.
(2008) - et al.
Molecular mechanisms of hepatocellular carcinoma
Hepatology
(2008) - et al.
Endogenous microRNA sponges: evidence and controversy
Nat. Rev. Genet.
(2016) - et al.
The roles of microRNA in cancer and apoptosis
Biol. Rev.
(2009)
MicroRNA-885-3p inhibits the growth of HT-29 colon cancer cell xenografts by disrupting angiogenesis via targeting BMPR1A and blocking BMP/Smad/Id1 signaling
Oncogene
MicroRNA 885-5p inhibits hepatocellular carcinoma metastasis by repressing AEG1
OncoTargets Ther.
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