KR101665753B1 - Composition comprising miRNA 675 for suppressing production of melanogenesis - Google Patents

Abstract

The present invention relates to a composition for inhibiting melanin production comprising miRNA 675 or a mimic thereof as an active ingredient, a composition for preventing or treating skin hypercholesterolemia, and a composition for skin whitening. MiRNA 675 or its mimetic according to the present invention inhibits the expression of tyrosinase, Trp-1, Trp-2 and MITF in melanocytes and inhibits phosphorylation of CREB, ERK, AKT and NF-κB signaling systems associated with melanin production And has an excellent effect of inhibiting the expression of tyrosinase and MITF in an animal model. Therefore, it is useful as a composition for inhibiting melanin production, a composition for preventing or treating skin hypercholesterolemia caused by excessive production of melanin, and a composition for skin whitening Lt; / RTI >

Description

A composition for inhibiting melanogenesis comprising miRNA 675 as an active ingredient {Composition comprising miRNA 675 for suppressing production of melanogenesis}

The present invention relates to a composition for inhibiting melanin production comprising miRNA 675 or a mimic thereof as an active ingredient.

The skin color of a person depends on various factors, especially season, race, and sex, and is mainly determined by the amount of melanin, carotene, and hemoglobin, and melanin is the most crucial factor. Melanin is synthesized in the melanocytes in the basal layer of the skin and transformed into peripheral keratinocytes to show human skin color. When melanin is abnormally low, skin lesions such as vitiligo are induced. On the other hand, it is known that when melanin is produced excessively, it forms spots and dullness. Melanin is produced by the action of tyrosinase, an amino acid, tyrosine, which is activated by ultraviolet light, so the skin becomes black when exposed to a lot of sunlight. Skin hyperkeratotic diseases due to melanin overgrowth include genetic skin diseases such as acquired skin diseases such as stains and skin diseases caused by medication such as minocycline, bleomycin, vesicopter, zidovudine, and skin diseases caused by infection For example, there is a playground. Cosmeceuticals of the concept of skin whitening effect form a big market in domestic and Japan, and these are the products which are combined with the substances which have the effect of inhibiting the activity of tyrosinase.

Recently, the activity of many enzymes related to melanin synthesis and skin lightness has become clear, but the reason why Asian skin is particularly susceptible to deposition and aging is not fully understood. The substances that are considered to reveal skin tone are typically known to inhibit melanin synthesis and the enzymes involved.

Conventionally, raw materials to be incorporated into whitening cosmetics as an activity inhibitor of tyrosinase include not only plant extracts such as ascorbic acid (vitamin C) and derivatives thereof, extracts of manganese bark extract, green tea extract, aloe extract and gold extract, but also kojic acid, arbutin, And niacinamide. However, various plant extracts are unstable, and when compounded in a product, the effect is not persistent, and the ability to inhibit tyrosinase activity is also insufficient. In addition, kojic acid is commonly used as a tyrosinase inhibitor but can cause an allergic reaction (Nakagawa M. et al., Contact Dermatitis, 43: PP9-3 (1995) And thus it is difficult to prepare it as a composition. Niacinamide is a water-soluble vitamin B3, also known as nicotinamide, as a whitening functional agent recently approved by the Food and Drug Administration. Niacinamide does not inhibit tyrosinase and opioxidase in contrast to conventional inhibition of melanin synthesis of melanin synthesis inhibitors. As a result of experiments with melanocyte cultures, niacinamide does not show any inhibition of melanin synthesis, but merely synthesizes melanin cells located in the basal membrane It is known that melanosomes loaded with melanin are transferred from melanocytes to keratinocytes through water dendrites and eventually block the pathway to the skin surface. However, it is known that niacin acetic acid used as an intermediate in the manufacture of niacinamide has a high level of cytotoxicity when it is left at a certain level (about 20-100 PPM) when the niacinamide is purified at a high purity in the process.

As a result of continuing research to find a novel substance which inhibits melanogenesis and inhibits skin whitening and stroma formation, the present inventors have found that miRNA (microRNA) 675, or its mimic, The present inventors have completed the present invention by confirming that there is an excellent effect of suppressing the activity of tyrosinase and inhibiting melanin production.

It is an object of the present invention to provide a composition for inhibiting melanin production comprising miRNA 675 or a mimic thereof as an active ingredient.

It is still another object of the present invention to provide a composition for preventing or treating skin hyperkeratotic disease comprising miRNA 675 or a mimetic thereof as an active ingredient.

Another object of the present invention is to provide a skin whitening composition comprising miRNA 675 or a mimetic thereof as an active ingredient.

In order to solve the above problems, the present invention provides a composition for inhibiting melanin production comprising miRNA 675 or a mimic thereof as an active ingredient.

In addition, the present invention provides a pharmaceutical composition for preventing or treating skin hyperkeratotic disease, comprising miRNA 675 or a mimetic thereof as an active ingredient.

The present invention also provides a food composition for preventing or ameliorating a skin hypercholesterolemia comprising miRNA 675 or a mimetic thereof as an active ingredient.

The present invention also provides a skin whitening cosmetic composition comprising miRNA 675 or a mimetic thereof as an active ingredient.

The present invention also provides a skin whitening food composition comprising miRNA 675 or a mimetic thereof as an active ingredient.

MiRNA 675 or its mimetic according to the present invention inhibits the expression of tyrosinase, Trp-1, Trp-2 and MITF in melanocytes and inhibits phosphorylation of CREB, ERK, AKT and NF-κB signaling systems associated with melanin production And has an excellent effect of inhibiting the expression of tyrosinase and MITF in an animal model. Therefore, it is useful as a composition for inhibiting melanin production, a composition for preventing or treating skin hypercholesterolemia caused by excessive production of melanin, and a composition for skin whitening Lt; / RTI >

FIG. 1 is a graph showing the expression level of intracellular tyrosinase when the miRNA-675 mimic or inhibitor is transfected into keratinocytes and co-cultured with normal melanocytes.
FIG. 2 is a graph showing the expression level of intracellular tyrosinase when miRNA-675 mimic or inhibitor is transfected into fibroblasts and co-cultured with normal melanocytes.
FIG. 3 is a graph showing the expression levels of intracellular tyrosinase, Trp-1, Trp-2 and MITF after transfection of miRNA-675 mimic or inhibitor into melanocytes.
4 is a graph showing the degree of phosphorylation of intracellular CREB, ERK, AKT and NF-kB after miRNA-675 mimetics or inhibitors were transfected into melanocytes.
5 is a graph showing the degree of intracellular H19 expression after miRNA-675 mimetic is transfected into keratinocytes.
6 is a graph showing the degree of intracellular H19 expression after miRNA-675 mimetic is transfected into melanocytes.
FIG. 7 is a graph showing the degree of H19 expression in cells after miRNA-675 mimetic is transfected into fibroblasts.
8 is a graph showing luciferase activity in 293 T cells transfected with pMIR-MITF and miR-675.
9 is a graph showing luciferase activity in melanocytes transfected with pMIR-MITF and miR-675 together.
FIG. 10 shows mRNA expression levels of MITF, tyrosinase, Trp-1 and Trp-2 in the skin of an animal model injected with miR-675 3p.
FIG. 11 is a graph showing the degree of expression of tyrosinase in skin of an animal model injected with miR-675 3p through immunohistochemical analysis.
FIG. 12 shows immunohistochemical analysis of the expression level of MITF in the skin of an animal model injected with miR-675 3p.

Hereinafter, the present invention will be described in detail.

The present invention provides a composition for inhibiting melanin production comprising miRNA 675 or a mimic thereof as an active ingredient.

The present invention also provides a composition for preventing or treating skin hyperkeratotic disease comprising miRNA 675 or a mimetic thereof as an active ingredient.

The present invention also provides a skin whitening composition comprising miRNA 675 or a mimetic thereof as an active ingredient.

The composition includes a pharmaceutical composition, a food composition, and a cosmetic composition.

In the present invention, miRNA (microRNA) is a regulatory RNA molecule regulating the expression of a gene at a post-transcriptional stage through base linkage with a 3 'untranslated region (UTR) site of mRNA, and is about 20-25 nucleotides nt) non-translated RNA. MicroRNAs have been implicated in the crucial biological processes associated with development, differentiation, apoptosis and proliferation (Cell 2004; 116: 281-97, Curr Opin Genet Dev 2005; 15: 410-5), as well as diabetes, neurodegenerative diseases and cancer (Nature 2004; 432: 226-30, Nat Cell Biol 2004; 6: 1048-53, Nature 2005; 435: 834-8).

In the present invention, miRNA 675 may be derived from a human (Genbank Accession No. NR_030533) or a mouse (Genbank Accession No. NR_030416), but is not limited thereto.

MiRNA 675 or its mimetic according to the present invention inhibits the expression of tyrosinase, Trp-1, Trp-2 and MITF in melanocytes and inhibits phosphorylation of CREB, ERK, AKT and NF-κB signaling systems associated with melanin production And has an excellent effect of inhibiting the expression of tyrosinase and MITF in an animal model. Therefore, it is useful as a composition for inhibiting melanin production, a composition for preventing or treating skin hypercholesterolemia caused by excessive production of melanin, and a composition for skin whitening Lt; / RTI >

The skin scleroderma disease may be selected from the group consisting of genetic skin diseases such as acquired skin diseases such as spots, skin diseases caused by drug treatment, such as minocycline, bleomycin, vesicopter, zidovudine, But is not limited to, e.g.

The pharmaceutical compositions of the present invention may further comprise suitable carriers, excipients and diluents conventionally used in the manufacture of pharmaceutical compositions.

The pharmaceutical composition of the present invention can be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols or the like, oral preparations, suppositories and sterilized injection solutions according to a conventional method .

Examples of carriers, excipients and diluents that can be contained in the pharmaceutical composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like. Such solid preparations are prepared by mixing at least one excipient such as starch, calcium carbonate, sucrose, lactose, It is prepared. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included . Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.

The pharmaceutical composition of the present invention can be administered orally or parenterally, and when administered parenterally, it can be administered by intravenous injection, subcutaneous injection, muscle injection, intraperitoneal injection, transdermal administration, and the like.

The preferred dosage of the composition according to the present invention varies depending on the condition and body weight of the individual, the degree of disease, the type of drug, the route of administration and the period of time, but may be suitably selected by those skilled in the art, and preferably 0.001 to 100 mg / kg. The administration may be carried out once a day or divided into several times. The dose is not intended to limit the scope of the invention in any way.

In addition, miRNA 675 or mimetic thereof according to the present invention may be added to foods or beverages for the purpose of preventing or ameliorating skin hypercholesterolemic diseases, skin whitening. Examples of the foods include various foods, beverages, gums, tea, vitamin complexes, functional foods, and the like. Specific nutritional foods (eg, crude oil, spirits, baby food, etc.) (Eg soy sauce, soybean paste, hot pepper paste, mixed sauce, etc.), sauces, confections (eg, snacks), candies, chocolates, gums, ice cream, dairy products , Fruit drinks, vegetable beverages, fermented beverages, etc.) and natural seasonings. The food, beverage or food additive may be prepared by a conventional production method.

The term "functional food" as used herein refers to a food group that is imparted with added value to function or express the function of the food by physical, biochemical, biotechnological techniques, etc., or to control the biological defense rhythm of the food composition, Means a food which has been designed and processed so as to sufficiently express the body's control function with respect to the living body. Specifically, it may be a health functional food. The functional food may include a food-acceptable food-aid additive, and may further comprise suitable carriers, excipients and diluents conventionally used in the production of functional foods.

The amount of miRNA 675 or mimetic thereof in the food or beverage may comprise from 0.001% to 90% by weight, preferably from 0.1% to 50% by weight of the total food, And may be in the range of 0.001 g to 2 g, preferably 0.01 g to 0.1 g, based on the total weight of the composition. However, in the case of long-term ingestion intended for health and hygiene purposes or health control purposes, There is no problem in terms of safety, so it can be used in an amount more than the above range, so it is not limited to the above range.

The food composition of the present invention may contain various flavors or natural carbohydrates as an additional ingredient like a normal food composition. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And polysaccharides such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. The above-described flavors can be advantageously used as natural flavorings (tau martin), stevia extracts (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.).

The food composition may contain flavors such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, colorants and heavies (cheese, chocolate etc.), pectic acid and its salts, alginic acid and its salts, , Protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks, and the like.

In addition, miRNA 675 or mimetic thereof according to the present invention can be added to functional cosmetics for the purpose of preventing or ameliorating skin hypercholesterolemia and for skin whitening.

The cosmetic of the present invention can be produced in the form of a general emulsified formulation and a solubilized formulation. Cosmetics of emulsified form include nutrition lotion, cream, essence, etc., and cosmetics of solubilized form have softening longevity. Examples of formulations of cosmetics suitable for the present invention include solutions, gels, solid or kneaded anhydrous products, emulsions obtained by dispersing oil phase in water phase, suspensions, microemulsions, microcapsules, microgranules or ionic forms (liposomes) May be provided in the form of a follicular dispersing agent of the type, cream, skin, lotion, powder, ointment, spray or conical stick. It can also be prepared in the form of a foam or an aerosol composition further containing a compressed propellant.

The cosmetics of the present invention may further comprise one or more of a fatty substance, an organic solvent, a solubilizing agent, a thickening agent and a gelling agent, a softening agent, an antioxidant, a suspending agent, a stabilizer, a foaming agent, a fragrance, a surfactant, Such as fillers, emulsifiers, emulsifiers, fillers, sequestering and chelating agents, preservatives, vitamins, blockers, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, lipid vesicles or any other ingredient commonly used in cosmetics May contain adjuvants commonly used in the field of cosmetics or dermatology. And, the above ingredients can be introduced in amounts commonly used in the field of dermatology.

MiRNA 675 or mimetic thereof of the present invention may be contained in an amount of 0.001 to 30% by weight based on the total weight of the cosmetic composition, but is not limited thereto.

Hereinafter, the present invention will be described in more detail with reference to examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.

Example 1: Determination of the effect of mimic of miRNA-675 on melanin production

In order to confirm the effect of mimic of miRNA-675 on melanogenesis, the following experiment was carried out. First, miRNA-675 mimetics or inhibitors were transfected into keratinocytes or fibroblasts, co-cultured with normal melanocytes, or directly transfected into melanocytes. As a control, a microRNA mimetic (Dhmarcon Research, Lafayette, CO) was used, and a human miRNA-675 mimetic was purchased from Dhmarcon. Transfection was performed using the TransITsiQUEST transfection reagent (Mirus, PanVera, Madison, Wis.) According to the manufacturer's instructions. After obtaining the protein from each cell to which the transfection was performed, the same amount (20 μg) of the protein was separated using 10% SDS-PAGE and transferred to a nitrocellulose membrane. PKK, pKK, pKK, GSK, pKK, pKK, pKK, pKK, pKK, pKK, pKK, pKK, mouse HRP (horseradish peroxidase (HRP)) was incubated with the primary antibody, polyclonal (Cell Signaling Technology, Beverly, Mass., USA) or with primary antibody for tyrosinase (Santa Cruz Biotechnology, Santa Cruz, Calif. ) -Fused secondary antibody (Santa Cruz Biotechnology). After that, each membrane was treated with chemiluminescence solution (Thermo, Rockford, IL, USA) for signal enhancement, and the expression of each protein was measured using Image Reader (LAS-3000; Fuji Photo Film, Tokyo, Japan) Respectively. The β-actin antibody was used to normalize the expression level of each protein. The results are shown in Fig. 1 to Fig.

As shown in FIGS. 1 and 2, when miRNA-675 mimetic was transfected into keratinocytes (FIG. 1) or fibroblasts (FIG. 2) and co-cultured with normal melanocytes, expression of tyrosinase .

As shown in FIGS. 3 and 4, the miRNA-675 mimetic was directly transferred to melanocytes. As a result, intracellular tyrosinase, Trp-1 (tyrosine-related protein-1), Trp-2 and MITF -associated transcription factor (FIG. 3) was decreased (FIG. 3), indicating that phosphorylation of CREB, ERK, AKT and NF-κB signal transduction systems related to melanin production was inhibited (FIG.

Example 2: Confirmation of effect of miRNA-675 on H19 expression level

In order to confirm the effect of miRNA-675 on the degree of H19 expression, the miRNA-675 mimetic was transfected into keratinocytes, melanocytes or fibroblasts, respectively, and RT (real time) -PCR To confirm the relative expression level of H19 RNA (normalized using the expression level of GAPDH). The results are shown in Figs. 5 to 7. Fig.

As shown in FIGS. 5 to 7, the miRNA-675 mimetic was transfected into keratinocytes (FIG. 5), melanocytes (FIG. 6) or fibroblasts (FIG. 7) There was no significant difference, confirming that the direct target of miRNA-675 was not H19.

Example 3: Effect of miRNA-675 on the degree of MITF expression

In order to confirm the effect of miRNA-675 on the degree of MITF expression, the following experiment was conducted. First, human MITF 3'UTR target positions were amplified using PCR (5'-GGACTAGTGAGACTTTAACGGAAACGCAAAG-3 'MITF-3UTR-F) and 5'-CCCAAGCTTTAAAATCAATCCAACTCTAGAAAAG-3' MITF-3UTR-R) -REPORT was cloned into the Luciferase gene downstream of the Luciferase vector (Ambion, Austin, Tex.) (PMIR-MITF). 293T cells or melanocytes were cultured in a 6-well plate, and the pMIR-MITF or pMIR-REPORT (control group) prepared in the above procedure was added to each well using a pRL-TK vector (Promega, Madison, Wis.) Using Lipofectamine 2000 (Invitrogen) and treated with 50 nM of miR-675. After 24 hours, Luciferase activity was measured using Dual-Luciferase Reporter Assay (Promega). The results are shown in Fig. 8 and Fig.

As shown in FIGS. 8 and 9, it was confirmed that the luciferase activity was markedly decreased in both 293 T cells (FIG. 8) and melanocytes (FIG. 9) transfected with pMIR-MITF and miR-675, MiRNA-675 inhibited the expression of MITF by targeting 3 'UTR (untranslated region) of MITF.

Example 4: Determination of the effect of miR-675 on melanogenesis in animal models

In order to confirm the effect of miR-675 on melanogenesis in an animal model, the following experiment was carried out. 5 μg of mouse miR-675 3p in the ear and back of C57BL / 6J female mice were injected under the epidermis with cationic polymer transfection reagent of in vivo-jetPEI ^™ (Polyplustransfection SA, Illkirch, France) . The control group was microRNA. The miRNA was injected three times at intervals of 24 hours. RT-PCR and immunohistochemical analysis were performed according to a conventionally known method using mouse skin tissue after the experiment. The results are shown in Figs. 10 to 12. Fig.

As shown in FIG. 10, RT-PCR revealed that mRNA expression of MITF, tyrosinase, Trp-1 and Trp-2 was decreased in mouse skin by miR-675 3p.

As shown in Figs. 11 and 12, immunohistochemical analysis revealed that the expression of tyrosinase (Fig. 11) and MITF (Fig. 12) decreased in mouse skin by miR-675 3p. From the above results, it was confirmed that miRNA-675 has an excellent effect of inhibiting melanogenesis in an animal model.

Hereinafter, formulation examples of the composition of the present invention will be described, but the present invention is not intended to be limited thereto but is specifically described.

Formulation Example 1. Preparation of a pharmaceutical composition

1-1. Manufacture of Powder

miRNA 675 or its mimic 2g

Lactose 1g

The above components were mixed and packed in airtight bags to prepare powders.

1-2. Injection preparation

RTI ID = 0.0 > miRNA 675 < / RTI &

180 mg mannitol,

Na ₂ HPO ₄ .12H ₂ O 26 mg

2974 mg of distilled water

After mixing the above components, an injection was prepared according to the usual production method.

Formulation Example 2. Preparation of Food Composition

2-1. Manufacture of Health Functional Foods

miRNA 675 or its mimic 100 mg

Vitamin mixture quantity

Vitamin A acetate 70 μg

Vitamin E 1.0 mg

Vitamin B1 0.13 mg

0.15 mg of vitamin B2

Vitamin B6 0.5 mg

Vitamin B12 0.2 μg

Vitamin C 10 mg

Biotin 10 μg

Nicotinic acid amide 1.7 mg

Folic acid 50 μg

Calcium pantothenate 0.5 mg

Mineral mixture quantity

1.75 mg of ferrous sulfate

0.82 mg of zinc oxide

Magnesium carbonate 25.3 mg

Potassium monophosphate 15 mg

Secondary calcium phosphate 55 mg

Potassium citrate 90 mg

Calcium carbonate 100 mg

Magnesium chloride 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.

Formulation Example 3. Preparation of cosmetic composition

3-1. Manufacture of softening longevity (skin lotion)

miRNA 675 or its mimic 0.5%

Beta-1,3-glucan 1.0%

Butylene glycol 2.0%

Propylene glycol 2.0%

Carboxyvinyl polymer 0.1%

Phage-12 nonyl phenyl ether 0.2%

Polysorbate 80 0.4%

Ethanol 10.0%

Triethanolamine 0.1%

Preservative, pigment, perfume

Purified water to 100%

3-2. Manufacture of nutrition cream

miRNA 675 or its mimic 1.0%

Beta-1,3-glucan 5.0%

Wax 10.0%

Polysorbate 60 1.5%

Pigment 60 Hardened castor oil 2.0%

Sorbitan sesquioleate 0.5%

Liquid paraffin 10.0%

Squalane 5.0%

Caprylic / capric triglyceride 5.0%

Glycerin 5.0%

Butylene glycol 3.0%

Propylene glycol 3.0%

Triethanolamine 0.2%

Preservative, pigment, perfume

Purified water to 100%

Claims (7)

A composition for inhibiting melanin production induced by the expression of tyrosinase or microphthalmia-associated transcription factor (MITF) comprising miRNA (microRNA) 675 as an active ingredient.
delete A pharmaceutical composition for preventing or treating skin hypercholesterolemia caused by the expression of tyrosinase or microphthalmia-associated transcription factor (MITF) containing miRNA (microRNA) 675 as an active ingredient.
[Claim 5] The pharmaceutical composition according to claim 3, wherein the scleroderma is a stigma or a spongiform encephalopathy.
A food composition for preventing or ameliorating skin hyperkeratotic diseases caused by the expression of tyrosinase or microphthalmia-associated transcription factor (MITF) containing miRNA (microRNA) 675 as an active ingredient.
A cosmetic composition for whitening skin by inhibiting the expression of tyrosinase or microphthalmia-associated transcription factor (MITF) containing miRNA (microRNA) 675 as an active ingredient.
A composition for skin whitening by inhibiting the expression of tyrosinase or microphthalmia-associated transcription factor (MITF) containing miRNA (microRNA) 675 as an active ingredient.

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