miR-124-3p Suppresses the Invasiveness and Metastasis of Hepatocarcinoma Cells via Targeting CRKL

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Majid, Abbasi (author)

miR-124-3p Suppresses the Invasiveness and Metastasis of Hepatocarcinoma Cells via Targeting CRKL

Article/chapterEnglish2020

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2020-09-15
Frontiers Media SA,2020

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LIBRIS-ID:oai:gup.ub.gu.se/296974
https://gup.ub.gu.se/publication/296974URI
https://doi.org/10.3389/fmolb.2020.00223DOI

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Language:English

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Subject category:art swepub-publicationtype

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Abnormal expressions of microRNAs are involved in growth and progression of human cancers including hepatocellular carcinoma (HCC). An adaptor protein CRKL plays a pivotal role in HCC growth, whereas miR-124-3p downregulation is associated with clinical stage and the poor survival of patients. However, the relationship between miR-124-3p and CRKL and the molecular mechanisms through which they regulate HCC metastasis remains unclear. In the current work, we explored miR-124-3p and its correlation with CRKL expression in HCC patient tissues. We found that miR-124-3p deficiency is inversely co-related with CRKL overexpression in tumorous tissues of HCC patients, which was also consistent in HCCLM3 and Huh7 HCC cell lines. Target validation data shows that miR-124-3p directly targets CRKL. The overexpression of miR-124-3p reverses the CRKL expression at both mRNA and protein levels and inhibits the cell development, migration, and invasion. Mechanistic investigations showed that CRKL downregulation suppresses the ERK pathway and EMT process, and concomitant decrease in invasion and metastasis of HCC cells. The expressions of key molecules in the ERK pathway such as RAF, MEK, ERK1/2, and pERK1/2 and key promoters of EMT such as N-cadherin and vimentin were downregulated, whereas E-cadherin, a key suppression indicator of EMT, was upregulated. MiR-124-3p-mediated CRKL suppression led to BAX/BCL-2 increase and C-JUN downregulation, which inhibited the cell proliferation and promoted the apoptosis in HCC cells. Collectively, our data illustrates that miR-124-3p acts as an important tumor-suppressive miRNA to suppress HCC carcinogenesis through targeting CRKL. The miR-124-3p-CRKL axial regulated pathway may offer valuable indications for cancer research, diagnosis, and treatment.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Cell- och molekylärbiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Cell and Molecular Biology hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Cancer och onkologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology hsv//eng
Hepatocarcinoma
Metastasis
microRNA

Added entries (persons, corporate bodies, meetings, titles ...)

Wang, Jinxia (author)
Nawaz, MuhammadGothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research(Swepub:gu)xnawmu (author)
Abdul, Sattar (author)
Ayesha, Munawar (author)
Guo, Chunmei (author)
Liu, Qinglong (author)
Liu, Shuqing (author)
Sun, Ming-Zhong (author)
Göteborgs universitetInstitutionen för medicin, avdelningen för reumatologi och inflammationsforskning (creator_code:org_t)

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In:Frontiers in Molecular Biosciences: Frontiers Media SA72296-889X2296-889X

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By the author/editor: Majid, Abbasi; Wang, Jinxia; Nawaz, Muhammad; Abdul, Sattar; Ayesha, Munawar; Guo, Chunmei; show more...; Liu, Qinglong; Liu, Shuqing; Sun, Ming-Zhong; show less...

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